Peroxisome Proliferator-Activated Receptors (PPAR) down-regulate the expression of pro-inflammatory molecules in an experimental model of myocardial infarction

Myocardial infarction (MI) has been associated with an inflammatory response and a rise in TNFα, interleukin (IL)-1β, and IL-6. Peroxisome proliferator-activated receptors (PPARs) promote a decreased expression of inflammatory molecules. We aimed to study if PPAR stimulation by clofibrate decreases inflammation and reduces infarct size in rats with MI. Male Wistar rats were randomized into three groups: control, MI + vehicle, and MI + clofibrate (100 mg/Kg). Treatment was administered three consecutive days, previous to 2 h of MI. MI induced an increase in protein expression, mRNA content, and enzymatic activity of inducible nitric oxide synthase (iNOS). Additionally, MI incited an increased expression of matrix metalloproteinase (MMP)-2 and -9, intercellular adhesion molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear factor-κB (NF-κB) and decreased IκB, both in myocyte nuclei and cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and -9, ICAM, IL-6, NF-κB, and IκB. Infarct size was smaller in clofibrate-treated rats compared to MI-vehicle animals. In silico analysis exhibited 3 motifs shared by genes from renin angiotensin system, PPAR-α, iNOS, MMP-2 and -9, ICAM-1 and VCAM suggesting a cross regulation. In conclusion, PPARα-stimulation prevents overexpression of pro-inflammatory molecules and preserves viability in an experimental model of acute MI.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author