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Table 8 POSITIVE EFFECTS OF PPARalpha AND PPARgamma AGONISTS

From: Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: The pleiotropic effects of folate supplementation

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.
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