heart news and views ...3 volume 16, number 1, 2008 paces by moderators and delegates, and provided...

1

http://ees.elsevier.com/jmcc/default.aspfor online submission

of manuscripts

Heart News

and views

Volume 16, Number 1, 2008

www.ishrworld.org

the news Bulletin of the International Society

for heart research

In this issue:

� Report from European Section

Meeting . . . . . . . . . . . . . . . . . . . . . . 1

� President's Letter . . . . . . . . . . . . . 4

� ISHR International Poster

Award . . . . . . . . . . . . . . . . .. . . . . . . 7

� Past Truth & Present Poetry,

by Richard J. Bing . . . . . . . . . . . . . 8

� In Memoriam . . . . . . . . . . . . . . . . . 10

� Report on Indian Section

Meeting . . . . . . . . . . . . . . . . . . . . . . 12

� 2007 Young Investigator

Award of the North American

Section . . . . . . . . . . . . . . . . . . . . . . 14

� Meetings Calendar . . . . . . . . . . . . 15

athens: ancient meets modern

athens,

greece

may 2008

14-1512-131-3

chandigarh,

india

february

2008

yia,

north

american

section

2007

Report from the

XXVIII European

Section Meeting

(May 28-31, 2008)

‘Future ages will wonder at us, as thepresent age wonders at us now’Pericles, General of Athens c. 495– 429 BC

Athens provided a wonderful location for the European Section meeting,offering an intriguing blend of novel science with historical interlude ina city rich in ancient history. A healthy balance of cardiovascular research

and cultural events ensured that the attendees enjoyed a stimulating visit to thecapital of this ancient civilisation. Modern medical practice originated fromHippocrates and Asklepieios, and from the evidence presented in Athens, moderncardiac science is flourishing in keeping with their ethic and energy.

Upon his arrival at the openingceremony, His Excellency the

President of the HellenicRepublic Dr Karolos Papoulias

is meeting Prof. Denis Noble,Prof. Evangelia Kranias (right)

and Prof. Guy Vassort (left).

2

the news bulletin of the international society for heart research

On arrival at Athens International Airport,the visitor is immediately struck by thedynamism of modern Athens thriving afterthe 2004 Olympic Games. Investment inmodern infrastructure continued to beapparent as one was whisked smoothlyfrom the airport to the city centre in themodern metro system which would be theenvy of any major world city. Few‘underground’ train systems can claim tobe educational, but travelling on Athens’subway allowed glimpses of ancient sitesuncovered during its construction, withdetailed descriptions for the passengerswaiting at each station platform. MegaronAthens International Conference centre,the location of the XXVIII meeting, is animpressive modern venue for a scientificmeeting, and upon our arrival both theclinical efficiency and generous hospi–tality of our hosts became apparent.Basking in the early summer Medi–terranean sun, Athens ensured a wel–coming and comfortable stay for all thedelegates visiting from near and far.

The conference started with a pre-symposium meeting addressing ThyroidHormones and the Heart, providing anintellectual appetiser before the maincourse ensued the following day. Theconference was opened in grand style inthe beautiful surroundings of the GreatHall of the National and Kapodistrian

University of Athens. This 19th centurybuilding has formed the heart of themodern University since its conceptionin 1837, and upon arrival delegates wereprovided with a welcome pack includinga copy of the Hippocratic Oath (in Greekand an English translation) and a CD ofHellenic Poetry and Music. The Presidentof Greece, Dr Karolos Papoulias was inattendence, and although he did notaddress the audience, his presence wascertainly felt with a plethora of securityguards and flash photography. Themeeting co-chairman, Professor DennisCokkinos, provided a stimulating andbalanced review of the Hippocratic Oath,its place in the evolution of the disciplineof Medicine, and its context in modernmedical practice. The choir from AthensUniversity Department of Music provideda relaxing interlude, and Professor DenisNoble from Oxford University waspresented with the ES/ISHR Medal ofMerit with an entertaining and humorouslaudatio provided by Professor GuyVassort. Few cardiac research scientistscan speak the number and diversity oflanguages in which Professor Noble haslectured! The recipient of the 2007 ES/ISHR Servier Fellowship, Dr Marta Roccio,presented her work on phenotypingcardiac progenitor cells, and Dr FrancescaRochais was awarded the new 2008 ES/ISHR Servier Fellowship. ProfessorEvangelia Kranias delivered an interestingKeynote Lecture highlighting her com–bined genotype-phenotype approach toheart failure, and introducing a number of

Prof. Denis Noble receives theMedal of Merit from Prof. Fabio diLisa, the outgoing President of theEuropean Section. The laudatio wasgiven by Prof. Guy Vassort (right).

new proteins into the central playing fieldof cardiomyocyte calcium cycling. Herlecture was preceded by a moving tributeby Lucie Carrier to Ketty Schwartz, whodevoted her life to a distinguished careerstudying heart and skeletal musclebiology, and sadly passed away lastDecember. We all retired to the courtyardof the Great Hall and had an opportunityto relax and enjoy the warm Athenianevening atmosphere, catching up withold friends and new over a glass of wine.

The scientific programme interspersedabstract presentations with overviews byleaders in the field, and, as usual, covereda diverse range of topics in cardiacresearch. Unfortunately, it is still notpossible to attend all the sessions, buthighlights for me included delineation ofthe paracrine hypothesis for bone marrowprogenitor cell-mediated cardiac repair, areview of I

f current and pharmacology,

and novel viewpoints on ryanodinereceptor regulation. The scientificprogramme was punctuated by plenty ofbreaks for mingling, informal scientificdiscussion and poster viewing. Over 250posters were presented during theconference, and, as usual, the diversityand inquisitive scientific methods ondisplay were testament to the strength ofscientific research in Europe (and beyond)in 2008. Presenters were put through their

Presentation of the 2008 ISHR-ES /SERVIER Research Fellowship by

Dr Stefano Corda (SERVIER, Paris)and Prof. Fabio di Lisa to

Dr Francesca Rochais.

3

volume 16, number 1, 2008

paces by moderators and delegates, andprovided new ideas in addition toconsolidating or questioning old hypoth–eses.

Professor David Eisner delivered the 2008Keith Reimer Lecture with his usualentertaining demeanor, using classicalmusic and Shakespearian poetry tohighlight the problems of love, despair,catecholamines and arrhythmias. Hereviewed his major contribution to theunderstanding of SR and transsarco–lemmal calcium cycling, and describedhow disrupting the tight regulation of thissystem can underpin arrhythmogenesisvia abnormal calcium release. The YoungInvestigators competition followed withthe usual high standard and wide scopeof topics. Mirna Chahine won the awardfor her presentation regarding thedifferential nuclear import of signaling invascular smooth muscle cells after LDLstimulation.

Two cultural lectures started the days’intellectual stimulation, and reflected thephilosophy of the host city. ProfessorDenis Noble discussed the ‘Music ofLife’ and integrating multilayered systemsbiology to suggest that perhaps our genesare prisoners rather than the governors.This provided an antidote to the ‘SelfishGene’ hypothesis, and (with musicalmetaphors, live music with French guitar,and a recital of O Sole Mio) introduced anovel perspective on life and biology. OnFriday we were treated to a historical touraround the Asklepieia, the hospices ofAsklepieios in Ancient Greece, byProfessor Stephanos Geroulanos. TheAsklepieia were the first medical centres,combining medical care with rehabilitationand religious support, and there wereover 400 centres throughout Greeceextending back to 1600BC. Prof. Gerou–lanos also gave us a flavour of medically-related art from Ancient Greece, whichincluded some eye-wateringly graphicpieces.

The evenings were an opportunity toappreciate some of Athens’ most famousmonuments. The Gala dinner was held in

a restaurant in the foothills of theAcropolis, overlooking the floodlitParthenon. As an enduring symbol ofancient Greece and of Athenian democ–racy, the Parthenon is one of the world’sgreatest cultural monuments and was atruly awe-inspiring backdrop to awonderful dinner. Professor Sian Hardingwelcomed all the delegates as the in–coming President of the ES-ISHR, andprovided the younger scientists with auseful template letter to reject the editorialrejection letter.

Friday evening provided an excursion toCape Sounio on the southernmost tip ofthe Attica Peninsula, where the Templeof Poseidon stands on the promontoryoverlooking the Aegean Sea. Legendstates that this is the location where

Aegeus, king of Athens, threw himself offthe cliff into the sea in the mistaken beliefthat his son, Theseus, had been killed bythe Minotaur. The temple is a Doric-styleperipteral temple with many columns stillpreserved, despite the graffiti from LordByron et al, and was referred to as HolySunium, the headland of Athens, inHomer’s Odyssey. After enjoying theview from top of the headland, we dinedon the beachfront with a breathtakingsunset across the sea. Traditional Greekdancers provided entertainment duringthe meal, and it ultimately proved toomuch for many delegates to resistparticipation on the dance floor.

Saturday concluded the scientificprogramme, with translational aspects ofcardiac science, a series of excellentpresentations showcasing the best ofGreek science, and the award of the YoungInvestigator and Poster prizes.

The organising committee should becommended for such a stimulating andwell-structured conference. In particular,Professor Cokkinos deserves specialmention for his tireless efforts in orga–nising and hosting the meeting, thesuccess of which was the result of hisenergy and enthusiasm.

Alex Lyon, MA, BM, BCh, MRCP

London, UK �

Prof. Bernard Swynghedauwon the dance floor with

one of the Greek dancersat Cape Sounio.

Prof. David Eisnerdelivered the 2008

Keith ReimerDistinguished Lec-ture and receives a

plaque fromProf. Sian Harding,

the incomingPresident of the

European Section.

4


president 's letter

E Pluribus Unum:

the New Covenant of the ISHR

Dear Colleagues,

In this column I would like to address an issue that I regard as vital for our Society,namely, that of unity. The structure of the ISHR is rather unusual among scientificsocieties, with an “International” Section and seven regional Sections (Australasian,Chinese, European, Indian, Japanese, Latin American, and North American), each

of which has its own separate governance and holds its own separate meetings. The relationship between the regionalSections and the International Section, and among the regional Sections themselves, has fluctuated over the years,undermined by uncertainty and punctuated by parochialism, competition, and, at times, outright tension. This is aproblem that most other cardiovascular societies don’t have, because they are not truly international. In this sense,it is the price we must pay for being the only truly international society devoted to cardiovascular research. Withmembers spread over five continents, it is inevitable that local issues take priority and the concept of being an“international” body may become nebulous or downright forgotten.

Many of us are aware of past instances of misunderstandings and friction between a regional Section and theInternational Section. In my mind, this has been one of the major problems that have plagued our Society. Althoughthe causes can be debated, it is difficult to dispute that the consequences have been nefarious for all involved.Fortunately, the dark times of regional–international tension seem to be finally over. Thanks to a number of changesin both the regional and the International Section, we have entered an era of détente, in which acrimony has been replacedby harmony. The World Congress in Bologna was the most tangible demonstration of this new world order. In anunprecedented show of unity, the European, Japanese, and North American Sections all held their annual meetingsin Bologna, and the Australasian and Latin American Sections sponsored symposia at the Congress. This was the firsttime in my memory that regional meetings were so fully integrated with the World Congress – an ecumenism that hasdoubtlessly benefited the Society in many ways (vide infra). The big question in 2007 was: will this last? The vastmajority of the colleagues with whom I spoke in Bologna and afterwards expressed fervent hope that the spirit of unitythat permeated Bologna 2007 would not be just a meteor.

It was not. I am pleased to report that a similar arrangement will be followed at the 2010 World Congress in Kyoto. Lastyear, the North American, Japanese and Australasian Sections announced that they will hold their 2010 regionalmeetings in Kyoto. Last May, the European Section decided to follow suit, and I wish to applaud their wise, enlightened,and forward-looking decision. Thus, in 2010 all major ISHR Sections will hold their meetings in conjunction with theKyoto World Congress. In another significant step forward for our Society, Masatsugu Hori, organizer of the Congress,has wisely decided to make Section-sponsored symposia an integral part of the Congress rather than separate satellitemeetings, which will further boost Congress attendance (i.e. attending both a Section meeting and the World Congresswill not increase total travel time).

Why is it so important that Section meetings be held in conjunction with World Congresses? The benefits are obvious.From the World Congress’ standpoint, this arrangement markedly increases attendance, making it possible to achievethat critical mass of delegates and speakers that is necessary to produce the scientific and social impact required fora meeting to be memorable. (It is self-evident that if regional meetings are held simultaneously with, or in closechronological proximity to, the World Congress, the participation of delegates and speakers in the Congress will bedecimated; as a consequence, its scientific program will be damaged and the ability of participants to interact with otherscientists will be curtailed.) Because networking is one of the main benefits of a scientific meeting, it is important that

5

our World Congresses be an opportunity for delegates to meet all, or almost all, of their fellow ISHR members, as wellas non-ISHR members. I am certain that those of you who attended the World Congress in Bologna found it to be anunforgettable scientific and cultural experience. This would not have been possible if, say, half of the delegates andspeakers had attended separate Section meetings instead of the Bologna Congress.

On the other hand, Sections also benefit handsomely from holding their meetings during the World Congress. The highscientific quality, the critical mass of scientists, the fervor and excitement that characterize a World Congress representunique experiences for the Section members who attend. (I still have fond memories of past World Congresses; inretrospect, I can say that these have been my most meaningful experiences with the ISHR.) There can be no doubt thata successful World Congress benefits the entire Society and, therefore, all of the Sections. Size does matter; none ofthe Sections can put together a program comparable to a World Congress in scope, depth, and richness of content.Furthermore, the World Congress highlights and leverages what I regard as one of our major strengths. That is, we havethe advantage over other cardiovascular societies that, by virtue of our international nature, we can hold WorldCongresses in attractive venues that are not accessible to most other cardiovascular organizations. As a result, ourWorld Congresses are characterized by a wonderful mix of outstanding science and exciting social programs. This israther unique. For example, one would be hard pressed to find another cardiovascular society that can boast a meetingwith a scientific and cultural value comparable to, say, the 2007 Congress in Bologna. It is self-evident that a successfulWorld Congress motivates delegates to renew their membership in, or to join, the ISHR, thereby benefiting the Sectionto which they belong. In short, outstanding World Congresses are one of the major benefits that a scientist gets forbeing a member of an ISHR Section.

In addition, combining Section meetings with the World Congress benefits the Society as a whole, for the WorldCongress is the only time when we all get together. Being in the same place at the same time reinforces the idea thatwe do belong to the same society. It allows interaction and exchange among Sections that otherwise would not evensee each other. This is critical to foster a feeling of cohesion. If we don’t do this, our sense of belonging to one societywill quickly evaporate.

In view of the above, the International Section has taken unprecedented steps to facilitate the merging of WorldCongresses with Section meetings. Recognizing that young investigators are not only the future of cardiovascularscience, but also the future of the ISHR, we have launched a new initiative aimed at promoting their participation inthe Kyoto Congress and their involvement in the Society. Specifically, I have proposed, and Council approved, adramatic expansion of the Trainee Travel Award Program, whereby in 2010 the International Section will distribute onehundred Trainee Travel Awards, each for US$ 1000, to support attendance at the Kyoto World Congress by students/Fellows. For the recipients of these awards, the cost of traveling to Kyoto should not be higher than what it would havecost to travel to a Section meeting in their own region. This program will enable many young investigators to enjoyan unforgettable scientific and cultural experience that otherwise would not be accessible to them. Such an initiativefulfills two of our core missions: our commitment to support young investigators and our efforts to help all ISHR Sectionsto hold their meetings during the World Congress. I am well aware that some ISHR members cannot afford travelingto a World Congress. However, this slight decrease in attendance is more than offset by the extraordinary opportunitythat is offered to Section members to experience a unique meeting and, in the case of Travel Award recipients, to doso at a relatively modest cost.

Returning to the broad issue of the regional-international Manichean ambivalence of the ISHR, how should we approachit? We must always keep in mind that our primary goal is to serve the ISHR members in the best possible way we can.This, in my mind, must be our overriding principle that takes precedence over anything else. To achieve this goal, itis my view that the ISHR needs both strong regional Sections and a strong International Section. We must realize thatboth contribute enormously to the Society. Regional Sections play a crucial role because they are the natural “home”for investigators in a specific country or continent. Nothing can replace this grassroots organization and activity.Sections offer many opportunities for scientific exchange, interaction, and involvement that would not be feasible atthe international level. Their relatively small meetings have a distinctive personal “feeling” and offer a quaint, familiar

Volume 16, Number 1, 2008

6

Roberto Bolli, M.D.President, ISHR

atmosphere that is highly conducive to networking. On the other hand, the International Section provides a numberof important services to the Sections and the membership at large, including an outstanding journal, memorable WorldCongresses, a well-organized website with many features, a splendid portfolio of awards that now includes three namedlectures and five prizes for every stage of an investigator’s career, one of the best newsletters I have seen in myprofessional experience, awards for best posters at Section meetings, and more. I believe ISHR members need a variedmenu that includes both the relatively small Section meetings (300-500 attendees) and, once every three years, a largerCongress (2,000-3,000 attendees). Thus, both the regional and the International Section serve the needs of themembership.

To summarize, we are one Society, not seven different Societies, and it is essential that all Sections work together tosupport the ISHR as a whole. If each Section holds separate meetings during World Congress years, the WorldCongresses will inevitably deteriorate and lose their appeal. This would be a disaster, for the World Congress is theflagship product of the ISHR; it is what defines us as a major international Society that is on a par with the AmericanHeart Association, the European Society of Cardiology, the Japanese Circulation Society, and other bodies. If the WorldCongress declines by losing attendance and speakers, the ISHR declines with it, and all Sections suffer. Conversely,strong World Congresses help to energize the entire Society, and therefore, the Sections as well. The experience of 2007eloquently attests to the benefits of combining Section meetings and World Congresses. We must not undo what hasbeen accomplished in Bologna. We must not go back to the dark days of competition between Section meetings andWorld Congresses. So, let us commit to carrying on the legacy of Bologna. Let us make 2007 the start of a new era forthe ISHR.

Ultimately, the vitality and success of the ISHR will require both vibrant Sections and a strong International Section,working together toward common goals. When we are divided, nobody wins, and all lose. That unity equals strengthhas been recognizes for ages across many diverse cultures. China is replete with old adages extolling the virtues of unity.“United we prevail, divided we fail”, “More bells, louder sound; more candles, brighter lights”, and “More firewood,higher flame” are but a few examples of a large anthology. I am told there are similar proverbs in India as well. The Italianhomologue is the saying “L’unione fa la forza” (“Unity strengthens”). And on the other side of the Atlantic, the officialmotto of the State of Kentucky is “United we stand, divided we fall”.

I ardently hope that the praxis of combining Section meetings and World Congresses will become permanent, andthat Bologna 2007 will pass in history as the beginning of a new covenant for the ISHR. We have no other choice, forunity is critical to our very survival as a viable cardiovascular society.

As always, I welcome your comments and/or suggestions at [email protected].


7


Beginning in 2009, the ISHR International Council will sponsor a Poster Award to be presented at Section meetings*and the World Congress. These awards will be given in addition to Section-sponsored poster awards and other younginvestigator awards that are currently offered at ISHR meetings.

Purpose of the PrizeThe purpose of the Poster Award is to call attention to the exceptional research presented in ISHR meeting postersessions, and to recognize outstanding young investigators whose posters demonstrate both excellence in researchand clarity of presentation.

Nature of the PrizeThe ISHR International Poster Award will be presented at the annual meetings of dues-paying ISHR Sections(*currently the North American, European, Japanese, Latin American and Australasian Sections) and the triennialWorld Congress. The winners will receive a certificate, a $300 prize and a ribbon to be displayed on the poster duringthe meeting.

Procedure for Application and Selection1. By intent, the Poster Award is targeted at young investigators, notably students and Fellows. Because ofinternational differences in the definition of “Fellow”, eligibility for the award is limited to those within 6 years of theirterminal degree (e.g. M.D. or Ph.D.).

2. Only ISHR members in good standing (as determined by their Section Secretary) will be eligible for the Award.

3. Applicants must be the first or last author of the abstract presented, and must be present at the meeting to be eligible.

4. Applicants must indicate their desire to compete for the Award when submitting their abstract to the meeting. Meetingorganizers will maintain a list of eligible posters.

5. The number of Poster Awards offered at a given meeting will be determined by the number of posters presented atthat meeting. One Award will be given for every 100 posters; at the larger meetings where multiple poster sessions areheld, this is expected to equate to one Award per day of poster presentation.

6. Posters will be evaluated by a small panel of senior investigators, selected and chaired by a member of the ISHRInternational Council who is in attendance at the meeting. The Secretary General will be responsible for providing thenames of the judges to the meeting organizer.

7. Poster presentations will be judged on the basis of:- Excellence and significance of research- Clarity of visual and verbal presentation

8. Council members will declare any conflict of interest (or close relationship with any candidate) and the votingmechanism will be adjusted accordingly.

ISHR International Poster Award

8


Past truth & present poetry

37. Heart failure and

ernest starling

Richard J. Bing

The treatment of human illness hasa selfish motivation: diseasemenaces not only the patient but

also the therapist, including the physicianand other professionals. All of us fear ourown vulnerability: “there but for the graceof God [go I].” The greater the menace,the greater the effort to conquer it. Thetreatment of heart failure represents oneof the great advances of modern medicine.Here, I describe some of our currentknowledge of heart failure, and tell thestory of one of the pioneers, ErnestStarling.

During the last fifty years, heart failurehas grown to epidemic proportions; it isa frequent cause of hospital admissions.Hospitals and medical schools havecreated new departments for its study,societies have been founded, and newjournals are being published. Seventy-five years ago when I was a medicalstudent, we learned that heart failurecauses edema, dyspnea and ascites, andthat the kidneys play a predominate role.I also remember listening to heateddiscussions: whether high and low outputfailure are related; is high output failure a“white raven?” Since then we havelearned that heart failure is a multi-systemdisease affecting ergoreceptors in skeletalmuscles, the sympathetic nervous andrenin-angiotensin systems with possibleparasympathetic withdrawal. Instead of“backward” and “forward” heart failure,we now distinguish between systolic anddiastolic heart failure. These two groupshave some common clinical features,although they have different mechanisms.Diastolic heart failure has become ofparticular clinical interest, since it afflictsat least half of the patients with heartfailure. The characteristic of diastolicheart failure is normal ejection fraction; atits basis are changes in the contractileelements of the heart muscle, leading tomalfunction of the heart, stiffness, andlack of plasticity. Echo-Doppler hasenabled us to explore diastolic failurethrough measuring mitral inflow velocity,

isovolumic relaxation time, and mitralinflow propagation velocity. In medicalschool we have learned that when heartmuscle stiffens, less volume is needed tocause a disproportionate pressure rise inthe cardiac cavities. Now we know thatstiffness of the ventricular muscle causesdiastolic dysfunction. In 1958, Kako andI studied the role of contractile elements,publishing experiments on isolatedactomyosin fibers from failing humanhearts; we found that they showeddiminished contractility. Now, thespotlight has turned on specific com–ponents of the contractile system,especially Tigrin (Connectin), the thirdmyofilament system in the sarcomere. Itsstiff isoform predominates when the heartmuscle is overloaded. It is likely thatincreased collagen turnover also con–tributes to cardiac stiffness. In my medicalschool days, treatment of heart failurewas restricted to digitalis leaf and oxygen.Since then, a series of discoveries havepaved the way to current treatmentregimens, beginning with ganglionicblocking agents and vasodilators. Thencame the discovery of orally activeangiotension-converting inhibitors, beta-blockers, and loop diuretics, the latterthanks to the pioneering work of Karl H.Beyer, who called the discovery ofchlorothiazide a classic example ofdesigned discovery. The use of angio–

tensin-inhibitors and beta-blockers hasbecome one of the significant advancesin modern medicine. Treatment withangiotensin-inhibitors is based on thework of Skeggs, who defined the renin-angiotensin system and discovered ACE,the converting enzyme, leading to thedevelopment of potent inhibitors. Bristowet al have shown that beta-adrenergicblockade selectively attenuates adren–ergic drive to the failing heart.

At a time when pathophysiology of heartfailure was primarily concerned withpressure, volume and flow, the Britishphysiologist, Ernest Starling (1866 – 1927),together with Patterson, discovered thelaw of the heart. It states that “themechanical energy set free on passagefrom the resting to the contracted statedepends on the area of the chemicallyactive surface, i.e. on the length of themuscle fibers” or, the output of the heartdepends on its diastolic filling. Starlingwas aware of similar results previouslyobtained by Otto Frank, Professor ofPhysiology in Munich, on the perfusedfrog heart. [I was a student of Frank inMunich, who was feared because he couldnot tolerate mediocrity amongst medicalstudents]. In his original report, Starlingplotted the venous pressure against thecardiac output, with the axes the wrongway. Henderson, in his book on Starling,ascribes this error to “unfamiliarity.”Maybe the great man simply made amistake, which escaped the eyes of theeditor of the Journal of Physiology. Itseems to happen to the best of us!

The law of the heart is graphicallyexpressed in left ventricular function orStarling curves, plotting volume outputagainst inflow pressure. The relevance ofthe Starling curves in heart failure hasbeen vehemently argued, like a theologicaldogma was disputed in the early middleages. One of the disputes was whetherthe curves of the failing heart have adescending limb. Some investigators haveanswered in the negative and have

9

aroused the anger of conservativephysiologists. But it is likely that in theailing heart the Starling curves are shiftedfrom normal, and that there exist familiesof curves, each one specific to the functionof a particular heart.

Aside from the law of the heart, Starling,with Bayliss, also defined the concepts oftranscapillary fluid dynamics and dis–covered the substance secretin, naming ita “hormone.” In addition to his scientificwork, Starling became involved in medicaleducation and managed to annoy Britishauthorities by his strong convictions,which he was unable to conceal. Duringthe First World War, he was com–missioned in the Army and devoted muchenergy to the war effort, but he laterresigned his commission and returned tohis laboratory. The life of this extra–ordinary man is unusual, not only becauseof his scientific accomplishments, but alsobecause of his strong personality. Thereis no question that Starling deserved theNobel Prize, but instead the prize went toPavlov, the Russian physiologist. It hasbeen recorded that members of the Nobelcommittee in Stockholm were swayed bypersonal feelings. Johan Erik Johannson,the chairman of the committee, haddeveloped some antipathy againstStarling, and Tigerstedt (of Renin dis–covery fame, also a member of thecommittee) had little confidence inStarling’s work. It is disappointing thatprejudice is found even amongst thosewho select the highest awards in science.Starling had a series of illnesses, and wasoperated on for cancer of the colon. Hisdeath occurred as he tried to recuperate inwarmer climates, sailing all alone to theWest Indies on a ship owned by a bananacompany. He believed that a sea voyageto a balmier climate would improve hishealth. But why a man with a loving familyand multiple ailments decided to go aloneon a sea voyage is a mystery. As Hen–derson wrote, “it is odd for a man, whothroughout his life was extraordinarilyfond of human company, to travel all byhimself.” The last part of the voyage wasbetween Puerto Limon and Kingston.

Ernest Starling died on board alonewithout family and friends.

What of the future treatment of heartfailure? In medicine and science there isnever an end point of knowledge, nor anend for the search for a cure. The searchgoes on and there are signs that newmodes of treatment may become available,such as phosphodiesterases and renininhibitors. For those of us with heartfailure, this is good news. To quoteStarling, “In physiology, as in all othersciences, no discovery is useless, nocuriosity misplaced or too ambitious, andwe may be certain that every advanceachieved in the quest of pure knowledgewill sooner or later play its part in theservice of man.”

ReferencesFloras JS. Clinical aspects of sympatheticactivation and parasympathetic withdrawalin heart failure. J Am Coll Cardiol 1993; 22:72A-84A.

Beyer KH. Chlorothiazide. Br J ClinPharmacol 1982; 13: 15-24.

Braunwald E. ACE inhibitors - a cornerstoneof the treatment of heart failure. N Engl J Med1991; 325: 351-353.

Nagendran J, Archer SL, Soliman D et al.Phosphodiesterase type 5 is highly expressedin the hypertrophied human right ventricle,and acute inhibition of phosphodiesterasetype 5 improves contractility. Circulation2007; 116: 238-248.

Katz AM, Zile MR. New molecular mechanismin diastolic heart failure. Circulation 2006;113: 1922-1925.

Ponikowski PP, Chua TP, Francis DP et al.Muscle ergoreceptor overactivity reflectsdeterioration in clinical status and cardio–respiratory reflex control in chronic heartfailure. Circulation 2001; 104: 2324-2330.

Granzier HL, Labeit S. The giant proteinTitin: A major player in myocardial mechanics,signaling, and disease. Circ Res 2004; 94: 284-295.

Van Heerebeek L, Borbely A, Niessen HWMet al. Myocardial structure and function differin systolic and diastolic heart failure.Circulation 2006; 113: 1966-1973.

Borbely A, van der Velden J, Papp Z et al.Cardiomyocyte stiffness in diastolic heartfailure. Circulation 2005; 111: 774-781.

Kako K, Bing RJ. Contractility of actomyosinbands prepared from normal and failing humanhearts. J Clin Invest 1958; 37: 465-470.

Martos R, Baugh J, Ledwidge M et al. Diastolicheart failure: Evidence of increased myocardialcollagen turnover linked to diastolic dys–function. Circulation 2007; 115: 888-895

Lester SJ, Tajik AJ, Nishimura RA et al.Unlocking the mysteries of diastolic function:Deciphering the Rosetta Stone 10 years later.J Am Coll Cardiol 2008; 51: 679-689.

Zegers ES, Verheugt FWA. Hotline sessionsof the 29th European congress of cardiology.Eur Heart J 2007; 28: 2799-2802.

Nguyen G, Delarue F, Burcklé C et al. Pivotalrole of the renin/prorenin receptor inangiotensin II production and cellularresponses to renin. J Clin Invest 2002; 109:1417-1427.

Skeggs LT, Kahn JR, Lentz K et al. Thepreparation, purification, and amino acidsequence of polypeptide renin substrate. JExp Med 1957; 106: 439-453

Henriksen JH. Ernest Henry Starling (1866-1927): the scientist and the man. J Med Biogr2005; 13: 22-30.

Sarnoff SJ, Berglund E. Ventricular function:I. Starling’s law of the heart studied by meansof simultaneous right and left ventricularfunction curves in the dog. Circulation 1954;9: 706-718.

Henderson J. A Life of Ernest Starling. NewYork: Oxford University Press. 2005.

Ahlqvist J. Ernest H. Starling and the NobelPrize. Scand J Clin Lab Invest 2003; 63: 315-316.

Richard J. Bing, M.D. �


10


KETTY SCHWARTZ, who diedon December 25, 2007, was one ofthe most emblematic figures of

cardiac and muscular research in thesecond half of the 20th and beginning ofthe 21st century. Her sensitivity, firmkindness, wisdom, natural authority, andthe beauty and warmth of her superbblue-eyed gaze will remain in the memoriesand hearts of all those who had the chanceto work with her, even if only for a fewdays or hours on one of the many boardsand committees she participated in. I hadthe chance to work with Ketty for 13 yearsthanks to Bernard Swynghedauw, the headof the Inserm Unit 127 in 1979, whoassigned me to her group to prepare myMaster in Science thesis. Actually, myplan at that time was to have a one yearbreak in my clinical training, but Ketty’soverwhelming charisma made it happendifferently! I finally found myself as apost-doc on Ketty’s team and, in 1985, Iwas offered the position of full timeresearch assistant! I left Ketty’s group atthe beginning of the nineties and eventhough, as a former clinician, I was happyto return to clinical cardiology much later,the years that I spent with Ketty wereundoubtedly the richest of my career.

Ketty was born on November 29, 1937 inBoulogne-Billancourt, a western suburbof Paris, in a family of emigrants runningaway from Nazi persecution. Probablyupon the advice of her family, who wantedher to have a good social situation, shestudied at the Paris Faculty of Pharmacyand received her diploma in 1960. Sheworked as a resident in pharmacy in Parispublic hospitals (1959-1964), an ex–perience that probably engendered herorientation towards a career dedicated topublic and state service rather than privatepractice . At the end of her internship, shewas recruited as a full time researcher forthe Centre National de la RechercheScientifique (CNRS), where she remaineda member her whole life; first as a ResearchAssistant, then as a Head of Researchand finally as a Director of Research, eventhough she spent most of her time workingfor the benefit of Inserm, either as a re-

searcher or at Inserm’s highest admin–istrative levels.

One of Ketty’s early mentors predictedthat, as a bright scientist, she would notspend more than 10 to 15 years workingon the same subject in the same place.This proved to be true. Ketty started herscientific career at the Laboratory ofBiochemistry of the CNRS Center forSurgical Techniques at the BroussaisHospital in Paris where she worked onheart and liver preservation and thedetection of rejection. During the midseventies, she was invited by BernardSwynghedauw to join him in creating anew Inserm unit dedicated to the bio–chemistry of cardiac remodeling andprogression to heart failure. Initiallylocated at the Faculty of Medicine, ruedes Saint-Pères in the Latin quarter, thegroup moved in 1978 to a new building atLariboisière Hospital near Gare du Nordto create the Inserm Unit 127. Owing tothe development of new sophisticatedimmunochemical and electrophoreticaltechniques, this collaboration initiated a

series of important discoveries; includingthe heterogeneity of cardiac myosin andthe redistribution of cardiac and skeletalmuscle myosin isoforms during devel–opment and in response to new functionalrequirements. At that time, Ketty’s groupincluded Anne-Marie Lompré, twotechnicians and me, plus one or two pre-graduate students. Ketty’s dedication tobench research and her commitment toher team created a unique environment;including both an open exchange of ideasthat led to progress in research, and amaternal atmosphere that imparted theimportant values of life: honesty, hardwork and discipline.

The mid eighties was the time of theeruption of molecular biology in cardio–vascular research, and Ketty was the firstwithin the French scientific cardiovascularcommunity to sense the importance ofthis methodological revolution as a meansto speed up research progress. The newtechniques were rapidly incorporated intoher investigative armament, resulting inimportant contributions in the areas ofnatriuretic peptides and Ca2+-ATPase ofthe sarcoplasmic reticulum (SR), includingthe first report of the decreased ex–pression of SR Ca2+-ATPase in the failinghuman heart. Interestingly, as predictedby her mentor, Ketty never spent muchtime over-exploiting the results of herresearch. When the first paper reportingan important new result was published,her mind had already moved to anotheridea, another question on the path ofknowledge. This brought her naturally tothe track of human genetics and to herdesire to contribute to deciphering genedefects responsible for a number ofcardiac and skeletal muscle familialdiseases. Indeed, Ketty had always beeninterested in comparative physiology andpathophysiology, and her work on cardiacmuscle was paralleled by similar work onskeletal muscle. In this respect, I rememberdiscussions we had during the lateeighties regarding the possible patho–physiology of the Syrian Hamstercardiomyopathy and, in fact, globalmyopathy, in which we proposed

in memoriam

ketty schwartz

1937-2007

11


hypotheses about alterations in forcetransduction between adjacent myocytesand myocyte degeneration long beforethe discovery of defects at the delta-sarcoglycan gene.

Eventually, Ketty’s involvement in theScientific Council of the AssociationFrançaise Contre les Myopathies (AFM)since 1986, her close friendship with thehead of the Association, Bernard Bara–taud, and two important scientists in thefield of skeletal muscle development anddisease, François Gros and MichelFardeau, and her desire to devote herresearch activity to the service of patientsand their families, combined to convinceher to leave the field of cardiac remodellingfor that of the genetics of heart and skeletalmuscle diseases. During the early nineties,this decision rapidly culminated in themain project of her scientific andprofessional life: the creation of an institutededicated to striated muscle physiologyand pathophysiology from bench tobedside, with a special focus on the careof young patients and their families. Sheleft Lariboisière and first joined the Insermunit of Michel Fardeau at the Fer à Moulin,a research site close to Pitié-SalpétrièreHospital, before being housed in thebasement of the cardiology building ofthe hospital owing to the support ofMichel Komajda and his interest in thepathophysiology of human cardio–myopathies. This started an era of veryfruitful collaboration between Ketty andclinical cardiologists, allowing France toparticipate successfully in the race to thediscovery of disease loci, genes andmutations, not only in the field ofcardiomyopathies but also in that ofchannelopathies owing to her closecollaborator, Pascale Guicheney. BecauseKetty always knew that identifying newmutations is nothing without under–standing the downstream pathophysio–logical mechanisms, she maintained aconstant interest in experimental models;for example, she closely followed the workof Lucie Carrier and Gisèle Bonne in theareas of myosin binding protein C andlamins, respectively.

After many years of waiting, Ketty andher group finally left the cardiologybuilding in 1996 to enter the brand newInstitut de Myologie. At this stage of hercareer, Ketty’s responsibilities were, ofcourse, far beyond those of a group leader,and she demonstrated outstanding skillsas an institute manager in developingfruitful interactions between basicscientists, clinicians, and researchadministrators resulting in a number ofmultidisciplinary research teams devotedto cardiac and skeletal muscle diseases inFrance and abroad. In addition, Kettybrought together patients and theirfamilies for a new constructive dialogueand partnership with researchers, phy–sicians and people in charge of publichealth. On the scientific side, in keepingwith her mentor’s prediction and alwaysin an attempt to serve the patients moredirectly, Ketty focused her interest onbiotherapies. She firmly supported anumber of researchers and fosteredseveral institutional initiatives in this area.She was personally involved in theorganization of the first cell therapy trialin patients with myocardial infarction thatinvolved a number of basic scientists andclinicians, including Jean-Thomas Vilquinand Philippe Ménasché to cite but a few.

After two terms on the Board of Governorsof the Inserm (1993-1996 and 2002-2005),her public career culminated in the positionof Director of Research at the FrenchMinistry of Research (2001-2002), whereshe exercised great influence on Frenchresearch policy through her strong willand outstanding capacity to find simpleand pragmatic solutions to the oftencomplex problems of French research.Ketty also played an important role in thegrowth and success of several inter–national organizations, most notably theInternational Society for Heart Research(ISHR). She served as a council member(1987-1995), and as the president of theEuropean Section (1992-1998), and, alongwith Bernard Swynghedauw and othercolleagues, she organised several mem–orable ISHR meetings in France. TheISHR was something like a family for Ketty,

in which she cultivated very strong anddurable friendships with, for instance,Jutta and Wolfgang Schaper, TomRuigrok, and a number of Israeli col–leagues. Israel had a very special place inher heart, and she made numerous trips toIsrael during the past ten years tocounteract attempts to boycott Israeliacademics. Ketty also served as theassociate editor of the Journal of Molec–ular and Cellular Cardiology (1985-1992)and of Circulation Research (1992-1999).

In addition to her personal scientificcontributions, Ketty undoubtedly par–ticipated in several major transitions incardiovascular research in France andelsewhere. There was the era before Ketty,and we are now in the era after Ketty, andwe all can see the important place sheoccupied both scientifically and in ourhearts. One of the reasons for this is that,despite all of her responsibilities, Kettyalways remained totally available for anyof her fellows or colleagues who neededher advice or support. In this advice,Ketty always favoured attitudes that shehad developed for herself: freedom,responsibility, creativity, and risk-taking.With Ketty’s death, I and some othershave lost a mother figure and a mentor,others have lost an inspiring colleague,and we all have lost an invaluable friend.

Jean-Jacques Mercadier, M.D., Ph.D.Paris, France �

12


Report on the Annual meeting of

the Indian Section of the ISHR

jointly held with the International

Academy of Cardiovascular Sciences

(Indian Section) and the Heart Failure

Society of India

(February 29 - March 2, 2008; chandigarh, india)

The Joint Annual meeting of the Indian Section of the ISHR, the InternationalAcademy of Cardiovascular Sciences (Indian Section) and the Heart

Failure Society of India was held at the Post Graduate Institute of MedicalEducation and Research (PGIMER), Chandigarh, from February 29th to March2nd 2008 under the chairmanship of Prof. KK Talwar. Prof. Madhu Khullar andDr Yashpal Sharma were the organizing secretaries of the meeting. Themeeting was attended by 250 delegates from all over the globe, and includedinvited talks by speakers from the USA, Canada, Japan, UK, the Netherlandsand Israel.

The meeting featured a series of lecturesin the fields of cardiomyopathy, cardio–vascular genomics, interventional car–diology, heart failure, metabolic syn–drome, molecular cardiology and pre–ventive cardiology. The scientific pro–gram was comprised of 16 sessions and 60invited talks on a wide range of topics incardiology. The meeting was an amalgamof clinical and basic cardiovascularresearch and provided a platform for the

interaction of cardiologists and basicscientists. The main topics of theconference were cardiomyopathies,genomics, rheumatic heart disease andheart failure. The role of herbal drugs incardiovascular medicine was also partof the program. The scientific ses–sions provided opportunities for younginvestigators to present their researchwork and interact with the renownedfaculty in their respective fields. Younginvestigators presented nearly 60 ab–stracts at the poster session and 20 oralpresentations at the awards session. The

Society initiated two awards to encouragescientific excellence by rewarding youngscientists who have distinguishedthemselves for their contributions tocardiovascular research.

The conference was inaugurated by theGovernor of Haryana, HE Dr AR Kidwai.The international faculty was introducedand welcomed with mementos by Prof.KK Talwar. Prof. NK Ganguly was awardedthe IACR Medal for his outstandingcontributions in the field of cardiovascularresearch. The highlight of the meetingwas the PL Wahi Oration, which wasdelivered by Prof. JL Mehta (USA) on therole of “Oxidative stress in athero–sclerosis”. The session was chaired byProf. KK Talwar and Prof. NK Ganguly.

Heart Failure was the main theme of themeeting and various aspects of etiology,pathophysiology and therapeutics werediscussed in several sessions. DrShainberg (Israel) spoke on metabolicaspects of heart failure. Dr AkiraMatsumori (Japan) discussed the sig–nificance of Hepatitis C virus in cardio–myopathies in Japan and various othercontinents including Pakistan and someparts of Europe. Dr IS Anand (USA)highlighted the role of anemia in heartfailure, while Dr S Sarkar (India) presenteda new transgenic model of heart failurethat mimicked human heart failure, and DrNS Dhalla (Canada) discussed thebenefits of treatment of congestive heartfailure by antiplatelet agents. Dr PK Singal(Canada), International coordinator forthis meeting, highlighted the role of drug-induced heart failure and its prevention,and Dr Narsimhan (India) presented abrief review on the role of device therapyin heart failure. Finally, Dr GS Chattwal(Germany) presented results on targeteddiagnosis of Streptococci capable ofcausing rheumatic fever.

The session on Molecular Cardiologyfocused on new and exciting findings inthe areas of stem cell therapy in dilatedcardiomyopathy, A-kinase anchor proteinAKAP121 in cardiac hypertrophy and

Prof. JL Mehta (USA) deliversthe Wahi Oration on the role ofoxidative stress in atherosclerosis

13


autophagy of cardiomyocytes in ischemiccardiomyopathy. A symposium on“Metabolic syndrome and cardiovasculardiseases” included talks on the role of Gprotein-coupled receptors in diabeticvascular complications (Dr P Ramarao,India), comparative efficacy of chromiumcomplex supplementation (Dr S Jain,USA) and the beneficial effects of non-selective beta blockers on the diabeticheart (Dr B Turan, Turkey). Dr RavinderS Kohli (USA) gave new insights intocomprehensive management of metabolicsyndrome.

Talks presented in sessions on “Hyper–tension” and “CAD” discussed thegenetic determinants and interactiveeffects of gene polymorphisms on therisk of hypertension and CAD, respec–tively. Dr N Mahapatra (India) describedchromogranin as a novel biomarker ofessential hypertension. Deficiency ofVitamin B12 compounded by abnor–malities in homoysteine metabolism which

might further elevate risk of CAD washighlighted by Dr S Sengupta (India).In addition, topics including preventivemeasures for ischemic heart disease,ethics in cardiovascular research,myocardial ischemia and angiogenesis,and the role of myocardial lymph–angiogenesis and its pathophysiology inheart diseases were covered in thescientific sessions.

The NS Dhalla Award for outstandingwork by young scientists in the area ofbasic cardiovascular research wasawarded to Mr Shamim Ahmad and MsBhoomoika Goyal for their presentationsentitled “Decreased expression of titin ispossibly an adverse effect of elevatedTNF-α in patient with dilated cardio–

myopathy” and “Effect of telmisartan oncardiovascular complications associatedwith STZ-induced Type I diabetic rats”,respectively.

The Nirmal K Ganguly Award, which isgiven for clinical research in the area of

cardiovascular diseases, was shared byDr Pretty Mathew and Dr Anuja Shah fortheir presentations entitled “Comparisonof closed loop control versus manualadministration of propofol using bispectralindex in cardiac surgery” and “Com–parison of primary aspiration of thrombususing aspiration catheter with con–ventional stenting in patients with STelevation myocardial infarction”, re–spectively. Dr R Kler and Mr Sumith RPanicker won awards for the best posters.

The scientific meetings were followed bya joyous cultural programme and bountifuldinners. These events brought themembers together to celebrate the successof the meeting and to enjoy typical Indiancuisine and Indian wines.

Dr Madhu KhullarChandigarh, India �

Dr NK Ganguly receivesthe IACR Medal for his

outstanding contributionsin the field of cardio-

vascular research

Delegates enjoy thefestivities at the

Gala Dinner

14


the myriad roles of micrornas

in heart disease

I was very honored to receive the Young Investigator Award of the North American Section at the 2007 XIX World Congress in Bologna, Italy, for my

work on the function of microRNAs (miRNAs) during heart disease. miRNAs aresmall, non-coding RNAs that negatively regulate gene expression in a sequence-specific manner by inhibiting mRNA translation or promoting mRNA degradation.My work led to the discovery of a network of miRNAs embedded in myosin heavychain genes, the dominant regulators of cardiac contractility, that controlscardiac and skeletal muscle gene expression, stress-responsiveness andcontractility.

Although originally from the Netherlands,in January 2005 I started my postdoctoraltraining in the lab of Eric Olson at theUniversity of Texas, SouthwesternMedical Center. Since it is becomingincreasingly clear that miRNAs are verypowerful regulators of human disease, Iam very excited to be in the unique positionto be able to extend our findings to a nextlevel as part of miRagen Therapeutics, anew biotech company initiated by EricOlson and others that focuses on thetherapeutic use of miRNAs in cardio–vascular disease.

MiRNA Function in Cardiac DiseaseThe heart responds to diverse forms ofstress by hypertrophic growth andreprogramming of cardiac gene expres–

sion, which culminate in a loss of pumpfunction, arrhythmias, and sudden death.MiRNAs are ~22-nucleotides in lengthand inhibit translation by interacting withthe 3' untranslated regions of specificmRNA targets. To date, the functions ofonly a handful of miRNAs have beendetermined, but their powerful effects oncellular phenotypes, impact on such asubstantial fraction of the genome, andevolutionary conservation across di–vergent species point to miRNAs as keyregulators of physiological and patho–logical processes.

Previously, we identified a signaturepattern of miRNAs that are dysregulatedduring pathological cardiac hypertrophyand heart failure in humans and mouse

models of heart disease. Gain- and loss-of-function studies in mice have revealedprofound and unexpected functions forthese miRNAs in the heart, including thecontrol of myocyte growth and identity,contractility, energy metabolism, andstress responsiveness, providing glimpsesof new regulatory mechanisms for heartdisease (Figure 1) (Ref. 1).

A hallmark of heart disease is the down-regulation of alpha-myosin heavy chain(MHC), a fast-contracting myosin, andup-regulation of beta-MHC, a slowmyosin, resulting in a diminution of cardiacfunction (Ref. 2). Previously, we showedthat a cardiac-specific miRNA (miR-208)encoded by an intron of the alpha-MHCgene is required for cardiomyocytehypertrophy, fibrosis and expression ofbeta-MHC in response to stress andhypothyroidism. miR-208 also repressesthe expression of fast skeletal musclegenes in the heart. Thus, the alpha-MHCgene, in addition to encoding the majorcardiac contractile protein, regulatescardiomyocyte growth, identity and geneexpression in response to stress andhormonal signaling through miR-208(Figure 2). These actions of miR-208 aremediated, at least in part, by THRAP1, athyroid hormone receptor coregulator thatis targeted for repression by miR-208 (Ref.3).

The MyomiR NetworkMore recently, we have discovered twomiR-208 related miRNAs encoded by otherMHC genes. This network of miRNAsembedded in MHC genes, which we

Figure 1. Induction of cardiac hypertrophy and heart failure by miR-195.H&E section of a heart of a wild type mouse and transgenic mice

expressing miR-195, a stress-inducible miRNA, under controlof the cardiac specific αMHC promoter.

Moderate levels of miR-195 expression cause cardiac hypertrophyand high levels of expression cause dilated cardiomyopathy

with ventricular dilatation and wall thinning.

Eva van Rooij

15


Figure 2. Requirement of miR-208 for cardiomyocytehypertrophy and fibrosis

A schematic diagram of a heart following thoracic aortic banding(TAB) is shown on the left.

Sections of hearts of wild type and miR-208 null mice are shownfollowing sham operation or TAB for 21 days.

High magnification views of the ventricular wall are shown at the bottom.Trichrome staining identifies fibrosis in blue.

Note that hypertrophy and fibrosis are diminished inmutant mice compared to wild type following TAB.

designated as the MyomiR network,represents an ancient mechanism for thecontrol of cardiac and skeletal musclegene expression and contractility. Ourrecent data indicate that it is actually themiRNAs hidden in the myosins thatthrough an intimate form of cross-talkregulate the expression of myosin genesthey are embedded in and thereby verypotently determine muscle function andremodeling in response to stress. Thisdiscovery offers powerful opportunitiesfor the therapeutic manipulation ofmiRNAs in the settings of cardiac andskeletal muscle disease.

Conclusions and Future DirectionsOur understanding of the biology ofmiRNAs is still in its infancy. With perhapsa thousand miRNAs encoded by thehuman genome, only a few of which havebeen studied in any detail, much remainsto be learned about the regulation andfunctions of miRNAs. An importantchallenge for the future will be to identifythe downstream targets that mediate theactions of miRNAs in development anddisease. The potent roles of miRNAs inthe heart’s stress response and in thecontrol of cardiac function and dys–function suggests opportunities for

ISHR MEETINGS CALENDAR

� August 7-10, 2008. XXXII Annual Meeting of the Australasian Section (jointly with the Cardiac Society of Australia and

New Zealand). Adelaide Conference Center in Adelaide, Australia. website www.sapmea.asn.au/conventions/csanz2008/

� October 20-24,2008. X Congress of the Chinese Section. Wenzhou, China. Website www.ishrivm.org

� November 8-12, 2008. Scientific Sessions of the American Heart Association. New Orleans, Louisiana.

website www.scientificsessions.org

� December 5-6, 2008. XXV Annual Meeting of the Japanese Section. Yokohama Kaiko Hall in Yokohama, Japan. Inquiries:

Dr Tohru Izumi, Convener, [email protected]

� May 26-29, 2009. XXXI Annual Meeting of the North American Section. Marriott Waterfront in Baltimore, Maryland.

website www.ishr2009.umaryland.edu

� May 30 -June 2, 2009. XXIX Annual Meeting of the European Section (jointly with the ESC Heart Failure Association). Nice,

France. website www.escardio.org/congresses/HF/HF2009

� May 13-16, 2010. XX World Congress of the ISHR. Kyoto, International Conference Hall, Japan

therapeutically exploiting the biology ofmiRNAs in the settings of congenital andacquired heart disease, especially forpathological cardiac remodeling.

References1. van Rooij E, Sutherland LB, Liu N, WilliamsAH, McAnally J, Gerard RD, Richardson JA,and Olson EN. Proc Natl Acad Sci 2006; 103:18255-18260.

2. van Rooij E, and Olson EN. J Clin Invest2007; 117: 2369-2376.

Eva van Rooij (Dallas, TX) was thewinner of the Young InvestigatorAward competition during the XXIXNorth American Section meeting atthe XIX ISHR World Congress (Bolo-gna, Italy; June 2007).

3. van Rooij E, Sutherland LB, Qi X,Richardson JA, Hill J, and Olson EN. Science2007; 316: 575-579.

Eva van Rooij, Ph.D.

Dallas, [email protected] �

16

HEART NEWS AND VIEWS

is the official News Bulletin of theInternational Society for HeartResearch and is published everyfourth month.

EditorL. Anderson LobaughDurham, NC, USAE-mail [email protected]

Founding EditorT.J.C. RuigrokWijk bij Duurstede, The NetherlandsE-mail [email protected]

Editorial BoardR.A. AltschuldColumbus, OH, USAM. AvkiranLondon, UKSecretary GeneralG. BaxterCardiff, UKEuropean SectionR. BolliLouisville, KY, USAPresidentT. IzumiKanagawa, JapanJapanese SectionH. KiriazisMelbourne, AustraliaAustralasian SectionX.Y. LiBeijing, ChinaChinese SectionA. MattiazziLa Plata, ArgentinaLatin American SectionE. MurphyBethesda, MD, USANorth American Section and TreasurerT. RavingerovaBratislava, Slovak RepublicA.-M.L. SeymourHull, UKN. TakedaTokyo, JapanK.K. TalwarChandigarh, IndiaIndian SectionD. EisnerManchester, UKEditor-in-Chief, JMCCB.J. WardLondon, UKK.T. WeberMemphis, TN, USA

Editorial Office3711 Lochn'ora ParkwayDurham, NC 27705USA.Phone/Fax: +1 919 493 4418


HEART NEWS AND VIEWSis published thanks to

an unrestricted grant from Servier

a private French pharmaceutical company committed to therapeutic advances in cardiovascular medicine as

well as other key therapeutic areas. We have successfullydeveloped products in the field of cardiovascular diseases(ischemic heart disease, hypertension, and heart failure),

as well as in other major therapeutic fields. A number of landmark studies like PROGRESS, EUROPA,

PREAMI, ADVANCE, HYVET, and BEAUTIFUL are, or have been, conducted with our support.

The dynamism of our research is ensured by consistentallocation of as much as over 25% of the annual turnover

of the Group to search for new molecules and develop their therapeutic applications.

Servier is also the founding father of The European

Cardiologist Journal by

Fax and Dialogues in

Cardiovascular Medicine,

a quarterly publication with a worldwide circulation edited by Roberto FERRARI

and David J. HEARSE.

Dialogues discusses in acomprehensive way issuesfrom the cutting edge of basic research and clinical cardiology.

Visit the web version at www.dialogues-cvm.org

The forthcoming issue, devoted to RISK FACTORS & CARDIOVASCULAR DISEASE

will feature articles by:

G.G. De Backer; R. De Vogli and M. Marmot; F. Paillard and J.C. Tardif; K. Schenck-Gustafsson

Risk Factors &

Cardiovascular Disease

Volume 13 • Number 2

2008

For further information on Dialogues in Cardiovascular Medicine please contact:

Dr Irina Elyubaeva - Servier International192 avenue Charles de Gaulle - 92578 Neuilly-sur-Seine Cedex - France

or [email protected]

heart news and views ...3 volume 16, number 1, 2008 paces by moderators and delegates, and provided...

Documents