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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 2; p. 270
• Main Authors: Ibarra-Lara, Luz, Sánchez-Aguilar, María, Soria-Castro, Elizabeth, Vargas-Barrón, Jesús, Roldán, Francisco J, Pavón, Natalia, Torres-Narváez, Juan C, Cervantes-Pérez, Luz G, Pastelín-Hernández, Gustavo, Sánchez-Mendoza, Alicia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-01-2019; MDPI
• Subjects: Animal models; Apoptosis; BAX protein; Bcl-2 protein; clofibrate; Coronary artery; Cytokines; Cytoplasm; Drug therapy; Echocardiography; Ejection fraction; Gelatinase A; Heart; Heart attacks; Heart failure; Inflammation; Inflammatory response; Intercellular adhesion molecule 1; Interleukin 6; Ischemia; Mitochondria; Myocardial infarction; Myocardium; NF-κB protein; Nitric-oxide synthase; PPARα; Proteins; reversion of damage; Structure-function relationships; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular cell adhesion molecule 1; Ventricle; ventricular remodeling; Myocardial infarction; ventricular remodeling; clofibrate; reversion of damage; PPARα; inflammation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24020270

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.