Table 8 POSITIVE EFFECTS OF PPARalpha AND PPARgamma AGONISTS

PPAR alpha: Lipid Effects

   a). Primarily a VLDL-Cholesterol (triglyceride) by increasing lipoprotein lipase and secondary LDL-Cholesterol lowering.

   b). HDL-cholesterol raising effect by increasing the expression of apo A-I and apo A-II. Positive outcomes of the Fibric acid (Gemfibrozil) (VA-HIT) and Fenofibrate (DAIS) studies.

PPAR gamma effects:

a). Primary Clinical Action : (Insulin Sensitizers). Improving insulin mediated glucose uptake.

b). Decrease thrombotic, inflammatory and oxidative changes that contribute to endothelial cell dysfunction.

c). Improve vascular reactivity.

d). Decrease plasminogen activator inhibitor-1 (PAI-1).

e). Decrease moncyte expression NFkappa-B.

f). Anti-inflammatory effects: Inhibition of macrophage activation and the production of inflammatory cytokines (TNFalpha, interleukin 6 and 1beta). New findings: May be through the effects of PPARdelta.

g). Decrease C-reactive protein and IL-6 (both markers of inflammation and cardiovascular risk). Dandonna P reference. Diabetes Technol Ther. 2002; 4(6): 809–15.

h). Inhibit vascular SMC migration and proliferation.

i). Lower blood pressure.

j). Attenuate myocardial hypertrophy and protect against ischemia-reperfuion injury.

k). Preserve pancreatic islet Beta cell function.

l). Attenuate (specifically rosiglitazone) oxidative and nitrative stress: enhanced PPAR gamma expression, improved endothelium – dependent vasodilation, preserved P-VASP, suppressed gp91(phox) of the membranous NAD(P)H Oxidase enzyme, reduced superoxide and total NOx (stable metabolic byproducts of NO) production, and inhibited nitrotyrosine formation.

m). Increase levels of Adiponectin.