PPAR[alpha] activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats

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...

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Bibliographic Details
Published inMolecular medicine reports Vol. 17; no. 5; p. 7218
Main Authors Yuan, Jie, Mo, Hongdan, Luo, Jing, Zhao, Suhong, Liang, Shuang, Jiang, Yu, Zhang, Maomao
Format Journal Article
LanguageEnglish
Published Spandidos Publications 01.05.2018
Subjects
Cell receptors
Development and progression
Genetic aspects
Myocardial ischemia
Physiological aspects
Reperfusion injury
China
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Summary: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 a (PPAR[alpha]) may inhibit ischemia/reperfusion damage by regulating stress reactions. The present study aimed to determine whether the activation of PPAR[alpha] 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 PPAR[alpha], 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 PPAR[alpha] 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 PPAR[alpha] 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. Key words: PPAR[alpha], cytoskeleton, desmin, acute MIRI, endoplasmic reticulum stress, calpain
ISSN:1791-2997
1791-3004
DOI:10.3892/mmr.2018.8771