Molecules (Jan 2019)

Clofibrate Treatment Decreases Inflammation and Reverses Myocardial Infarction-Induced Remodelation in a Rodent Experimental Model

  • Luz Ibarra-Lara,
  • María Sánchez-Aguilar,
  • Elizabeth Soria-Castro,
  • Jesús Vargas-Barrón,
  • Francisco J. Roldán,
  • Natalia Pavón,
  • Juan C. Torres-Narváez,
  • Luz G. Cervantes-Pérez,
  • Gustavo Pastelín-Hernández,
  • Alicia Sánchez-Mendoza

DOI
https://doi.org/10.3390/molecules24020270
Journal volume & issue
Vol. 24, no. 2
p. 270

Abstract

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Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.

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