1.Dr. Saurabh kr. Bajpai M.V.Sc. scholar Division- Animal Nutrition I.V.R.I. Bareilly

2. 1.Atherosclerosis definition 2.Risk factors in atherosclerosis 3.Atherosclerotic plaque formation 4.PUFAs 5.Role of PUFA in Atherosclerosis 6.New endogenous anti-inflammatory and proresolving lipid mediators 7.Conclusion 3. Atherosclerosis The thickening and hardening of arterial walls as a consequence of atheroma 4. Risk Factors in Atherosclerosis Major risk factors 1) Major Constitutional risk factors: i. Age ii. Sex 2) Major Acquired risk factors: i. Hyperlipidaemia ii. Hypertension iii. Diabetes mellitus 5. Minor Risk Factors: 1. Obesity 2. Hormones: Oestrogen deficiency 3. Physical inactivity 4. Stressful life 6. PUFAs PUFA stands for Poly-Unsaturated Fatty Acid. In chemical terms, that means that the fatty acid has more than one (poly) double bond in the carbon chain There are two main types of PUFAs omega-3 polyunsaturated fatty acids omega 6 polyunsaturated fatty acids. 7. Omega-3 Fatty Acids ALA C18:3 EPA C20:5 DHA C22:6 8. Omega-6 Fatty Acids Linoleic acid C18:2 Arachidonic acid C20:4 9. Protective role of n-3 PUFA in atherosclerosis 1. Resolationofinflammatoryprocess 2. Changeinbiologicalfunctionofcell membrane 3. Plaquestabalization 4. Changeinserumlipidprofile 5. Improvedflowmediatedarterialdilation 6. Antithrombotic 10. HOW n-3 PUFA reduses inflammation? Compete with n-6 fatty acids for prostaglandin and leukotriene synthesis Bind reactive oxygen species 11. Omega-3 F.A. Omega-3 F.A.Omega-6 F.A. Omega-6 F.A.CYCLOOXYGENASE/LIPOXYGENASE Pathway CYCLOOXYGENASE/LIPOXYGENASE PathwayPGE3,LTB5 PGE3,LTB5(anti-inflammatory) (anti-inflammatory)PGE2,LTB4 PGE2,LTB4(pro-inflammatory) (pro-inflammatory) 12. Bind with reactive oxygen species Decreased production of H2O2 Inhibition of nuclear factor-B system of transcription factors 13. n3- PUFA n3- PUFANF-B NF-BChemokines,Cytokines,ROS Chemokines,Cytokines,ROS Vasoconstriction Vasoconstriction Adhesion molecules Adhesion molecules Endothelial protection 14. Cytokines Cytokines ROS ROSNF-B NF-BChemokines&Cytokines Chemokines&Cytokines Vasoconstriction Vasoconstriction Adhesion molecules Adhesion molecules Endothelial dysfunction 15. 2.Change in biological function of cell membrane Incorporation of EPA and DHA in to CM Influences it,s organisation,fludity, and permeability Modulate K,Na,andCa channel activities Induction of NO release 16. 3.Plaque stabalization 17. 4.Change in serum lipid profile Omega-3 fatty acids decrease hepatic VLDLTG production and secretion Omega-3 fatty acids increase the conversion of VLDL to LDL particles 18. F.A.DGATVLDL-oxidationAcetyl CoAHDL 19. Anti-inflammatory and proresolving lipid mediators generated from PUFAs Lipoxins Resolvins Protectin Maresin 20. CONCLUSION Through their positive antithrombotic, lipidlowering, proendothelial functional activities, n-3 PUFAs play an important role on the mechanisms of atherosclerosis LC-n3-PUFAs significantly interact with inflammation-related mechanisms, such as endothelial activation, modification of eicosanoid metabolism, and resolution of the inflammatory process 21. REFERENCES 1.Emken EA. In: Proceedings from the Scientific Conference on Omega-3 Fatty Acids in Nutrition, Vascular Biology, and Medicine. Dallas, TX: American Heart Association, 1995, pp. 9-18. 2.Horrobin DF and Manku MS. In: Omega-6 Essential Fatty Acids. Horrobin DF, ed. New York, NY: Alan R. Liss, 1990, pp. 21-53. 3.Ferretti A and Flanagan VP. Prostaglandins Leukot Essent Fatty Acids. 1996;54:451-455. 4. Ratnayake WMN and Chen Z-Y. Lipids. 1996;31(Suppl):S279-S282. 5.Ackman RG and Cunnane SC. In: Advances in Applied Lipid Research. Padley FB, ed. London: JAI Press Ltd., 1992, pp. 167-215. 6. Houwelingen AC v and Hornstra G. World Rev Nutr Diet. 1994;75:175-178. 7. Salem Jr N, et al. Lipids. 1996;31(Suppl):S153-S156. 16. Brossard N, et al. Am J Clin Nutr. 1996;64:577-586.