Vascular effects of PPAR activation:

Inflammation

Campia U et al. Circulation. 2006;113:867-75.

Pioglitazone improves endothelial vasodilation and decreases inflammation

Forearm blood flow

(% from baseline) after

16 wks

N = 80 with hypertension or hypercholesterolemia and no diabetes

Pioglitazone 45 mg/d Placebo

100 200 400

600

500

400

300

0

Bradykinin (ng/min) All subjectsInsulin

resistantInsulin

sensitive

CRP (mg/L)

7

5

3

1

0

6

4

2

P = 0.0001

P = 0.38

P = 0.0008

P = 0.01

0

P = 0.41

P = 0.02

PPAR agonists impact inflammatory markers and adiponectin

N = 54 adults with metabolic syndrome and no diabetes

Samaha FF et al. Arterioscler Thromb Vasc Biol. 2006;26:624-30.

*P = 0.002; †P = 0.027; ‡P < 0.001

Change from

baseline after 12

weeks (%)

*

†

‡

Placebo Rosiglitazone 8 mg/d

IL-6CRP Adiponectin

-40

-20

0

20

40

0

50

100

150

200

Surrogate outcome results driving major TZD trials

TZDs are associated with reductions in atherosclerotic progression and restenosis

TZDs reduce inflammatory markers (CRP, TNF) independent of glycemic control

Reducing CV risk factors with TZDs may also reduceCV morbidity and mortality

Dormandy JA et al. Lancet. 2005;366:1279-89.