Novel benefits of peroxisome proliferator-activated receptors on cardiovascular risk

Purpose of review This review provides an overview of newly described mechanisms by which peroxisome proliferator-activated receptors (PPARs) (alpha, gamma, and delta) regulate several factors associated with cardiovascular risk. Recent findings PPAR agonists have known effects on plasma lipoprotein levels, inflammation, and insulin resistance all of which influence the risk of cardiovascular disease. Recent studies provide more detail regarding the mechanisms behind these changes. PPAR-alpha activation in the enterocyte on HDL and chylomicron formation. PPAR-gamma agonists reduce inflammation, in part, through direct effects on adipocytes and regulatory T cells within visceral adipose. PPAR-delta also has a relatively high expression in the macrophage. Incubation of macrophages with PPAR-delta agonists was shown to inhibit foam cell formation induced excessive levels of VLDL remnants. Summary Treatments that activate PPAR-alpha, PPAR-gamma, and PPAR-delta alone or in combination have the potential to reduce cardiovascular risk although multiple independent mechanisms. Treatment with PPAR agonists can reduce the burden of atherogenic postprandial lipoproteins and improve vascular function, reduce inflammation and inhibit foam cell formation. All of these would be expected to have favorable effects on cardiovascular risk. The challenge remains to develop compounds that maximize these potential cardiovascular benefits while minimizing undesirable effects of these compounds.