Mechanism of antiplatelet action of hypolipidemic, antidiabetic and antihypertensive drugs by PPAR activation PPAR agonists: New antiplatelet agents

Univ Talca, Fac Hlth Sci, Dept Clin Biochem & Immunohaematol, Interdisciplinary Excellence Res Program Hlth Agi, Talca, Chile. Fuentes, E (Fuentes, Eduardo); Palomo, I (Palomo, Ivan)Given the prevalence of cardiovascular disease in patients with cardiovascular risk factors (i.e., hypertension, diabetes, smoking and obesity) and that platelet activation plays an important pathogenic role in cardiovascular diseases, it is very important to identify the drugs that have multiple targets. In this sense, the present article describes the mechanism of antiplatelet action of hypolipidemic (statins and fibrates), antidiabetic (thiazolidinediones) and antihypertensive (nifedipine) drugs via peroxisome proliferator-activated receptor (PPAR) activation. The mechanism of antiplatelet action of the drugs is by direct activation of PPARs with the inhibition of cyclooxygenase-1, protein kinase C-alpha, calcium mobilization, thromboxane A2, sCD40L, platelet microparticles and cAMP-phosphodiesterase, and the stimulation of proteins kinase G and A Thus, these observations highlight PPARs as a novel therapeutic target for the treatment and prevention of cardiovascular diseases. (C) 2014 Elsevier Inc. All rights reserved