Attenuation of ER stress prevents post-infarction-induced cardiac rupture and remodeling by modulating both cardiac apoptosis and fibrosis

Tao Luo, Jin Kyung Kim, Baihe Chen, Ahmed Abdel-Latif, Masafumi Kitakaze, Liang Yan

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67 Scopus citations

Abstract

Endoplasmic reticulum (ER) stress is implicated in the pathophysiology of various cardiovascular diseases, but the role of ER stress in cardiac rupture and/or remodeling after myocardial infarction (MI) is still unclear. Here we investigated whether ER stress plays a major role for these processes in mice. We ligated the left coronary artery (LCA) without reperfusion in mice and administered either NaCl or 4-phenylbutyric acid (4-PBA, 20 mg/kg/d) intraperitoneally for 4 weeks. Cardiac rupture rates during the first week of MI were 37.5% and 18.2% in the control and 4-PBA groups, respectively. The extent of ventricular aneurysm and fibrosis was less, and the cardiac function better, in the 4-PBA group compared with the control group. The protein levels of ER stress markers in the heart tissues of the control group remained elevated during the entire 4-week period after MI, while pro-apoptotic proteins mainly increased in the early phase, and the pro-fibrotic proteins markedly increased in the late phase post MI; 4-PBA decreased all of these protein levels. In the primary cultured neonatal rat cardiomyocytes or fibroblasts, hypoxia (3% O2) increased the number of apoptotic cardiomyocytes and promoted the proliferation and migration of fibroblasts, all of which were attenuated by 4-PBA (0.5 mM). These findings indicate that MI induces ER stress and provokes cardiac apoptosis and fibrosis, culminating in cardiac rupture and remodeling, and that the attenuation of ER stress could be an effective therapeutic target to prevent post-MI complications.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalChemico-Biological Interactions
Volume225
DOIs
StatePublished - Jan 5 2015

Bibliographical note

Funding Information:
This study was supported by the grant from the Key Research Project of Natural Science Foundation of Guangdong Province, China (No. 05z002 , to Prof. Liang Yan). We thank Yanping Wang for excellent technical assistance.

Keywords

  • Apoptosis Fibrosis
  • Cardiac remodeling
  • Cardiac rupture
  • ER stress
  • Myocardial infarction

ASJC Scopus subject areas

  • Toxicology

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