期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 94, 期 6, 页码 634-642出版社
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/cjpp-2015-0356
关键词
PPAR; iNOS; fibrates; myocardial infarction; interleukins; cell adhesion molecules; matrix metalloproteinases; NF-kappa B; I kappa B
资金
- CONACyT (Consejo Nacional de Ciencia y Tecnologia, Mexico) [232874]
- CONACyT [222720]
Myocardial infarction (MI) has been associated with an inflammatory response and a rise in TNF-alpha, interleukin (IL)-1 beta, and IL-6. Peroxisome proliferator-activated receptors (PPARs) promote a decreased expression of inflammatory molecules. We aimed to study whether PPAR stimulation by clofibrate decreases inflammation and reduces infarct size in rats with MI. Male Wistar rats were randomized into 3 groups: control, MI + vehicle, and MI + clofibrate (100 mg/kg). Treatment was administered for 3 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 MMP-9, intercellular adhesion molecule (ICAM)-1, and IL-6. MI also elevated the nuclear content of nuclear factor-kappa B (NF-kappa B) and decreased I kappa B, both in myocyte nuclei and cytosol. Clofibrate treatment prevented MI-induced changes in iNOS, MMP-2 and MMP-9, ICAM-1, IL-6, NF-kappa B, and I kappa B. 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 alpha, iNOS, MMP-2 and MMP-9, ICAM-1, and VCAM-1, suggesting a cross regulation. In conclusion, PPAR alpha-stimulation prevents overexpression of pro-inflammatory molecules and preserves viability in an experimental model of acute MI.
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