PPARα activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats

• Published in: Molecular medicine reports Vol. 17; no. 5; pp. 7218 - 7226
• Main Authors: Yuan, Jie, Mo, Hongdan, Luo, Jing, Zhao, Suhong, Liang, Shuang, Jiang, Yu, Zhang, Maomao
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.05.2018; D.A. Spandidos
• Subjects: Acute Disease; Animals; Calpain; Cardiomyocytes; Coronary artery; Cytoskeleton; Cytoskeleton - metabolism; Cytoskeleton - pathology; Desmin; Desmin - metabolism; EKG; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Fenofibrate; Heart; Heart diseases; Homeostasis; Ischemia; Kinases; Laboratory animals; Lipids; Liver; Male; Metabolism; Microscopy; Morphology; Myocardial ischemia; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardium; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Physiology; PPAR alpha - metabolism; Protein expression; Proteins; Proteolysis; Pulmonary arteries; Rats; Rats, Wistar; Reperfusion; Rodents; Signal transduction; Studies; Therapeutic applications; Transmission electron microscopy; Ultrastructure
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2018.8771

The cytoskeleton serves an important role in maintaining cellular morphology and function, and it is a substrate of calpain during myocardial ischemia/reperfusion (I/R) injury (MIRI). Calpain may be activated by endoplasmic reticulum (ER) stress during MIRI. The activation of peroxisome proliferator‑activated receptor α (PPARα) may inhibit ischemia/reperfusion damage by regulating stress reactions. The present study aimed to determine whether the activation of PPARα protects against MIRI‑induced cytoskeletal degradation, and investigated the underlying mechanism involved. Wistar rats were pretreated with or without fenofibrate and subjected to left anterior descending coronary artery ligation for 45 min, followed by 120 min of reperfusion. Calpain activity and the expression of PPARα, desmin and ER stress parameters were evaluated. Electrocardiography was performed and cardiac function was evaluated. The ultrastructure was observed under transmission electron microscopy. I/R significantly induced damage to the cytoskeleton in cardiomyocytes and cardiac dysfunction, all of which were improved by PPARα activation. In addition, I/R increased ER stress and calpain activity, which were significantly decreased in fenofibrate‑pretreated rat heart tissue. The results suggested that PPARα activation may exert a protective effect against I/R in the myocardium, at least in part via ER stress inhibition. Suppression of ER stress may be an effective therapeutic target for protecting the I/R myocardium.