International Journal of Medical Sciences

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21 October 2017

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Int J Med Sci 2011; 8(7):564-572. doi:10.7150/ijms.8.564

Research Paper

Atorvastatin Inhibits Myocardial Cell Apoptosis in a Rat Model with Post-myocardial Infarction Heart Failure by Downregulating ER Stress Response

Xian Jing Song1,2, Chun Yan Yang1, Bin Liu2, Qun Wei1, Melvin T. Korkor1, Jie Yu Liu3, Ping Yang1✉

1. Department of Internal Medicine and Cardiology, China-Japan Union Hospital, Norman Bethune College of Medicine, Jilin University, China;
2. Department of Internal Medicine and Cardiology, Second Hospital, Norman Bethune College of Medicine, Jilin University, China;
3. Department of Internal Medicine and Endocrinology, Second Hospital, Norman Bethune College of Medicine, Jilin University, China

Abstract

Objective: To determine the effect of atorvastatin on rat heart failure after myocardial infarction and to investigate the underlying mechanism of atorvastatin-mediated myocardium protection.

Methods: Thirty-eight rats were randomly divided into three groups: a heart failure model group (model group), a heart failure plus atorvastatin treatment group (atorvastatin group) and a sham-surgery group (control group). The rat heart failure model was established by ligation of the left anterior descending of coronary arteries (LADs). Changes in hemodynamics parameters were recorded after the final drug administration. Plasma brain natriuretic peptide (BNP) concentration was determined by enzyme-linked immunosorbent assay (ELISA). Histological diagnosis was achieved by hematoxylin and eosin (H&E) and Masson's trichrome staining. The expressions of 78kDa glucose-regulated protein 78 (GRP78), caspase-12 and C/EBP homologous protein (CHOP, also known as GADD153) in myocardial cells and cultured cardiac myocytes were examined by Western blot. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to evaluate myocardial cell apoptosis, and flow cytometry was performed to examine the cell apoptosis of cultured cardiac myocytes.

Results: In the atorvastatin group, myocardial cells were lined up more orderly and myocardial fibrosis level was decreased compared to the model group. The expressions of GRP78, caspase-12 and CHOP in myocardial cells were decreased in atorvastatin group. Moreover, in the atorvastatin-treated group the cell apoptosis rate was reduced and the endoplasmic reticulum (ER) stress was activated in response to heart failure and angiotensin II(Ang II) stimulation.

Conclusions: By down-regulating GRP78, caspase-12 and CHOP expressions in myocardial cells in rat heart failure after myocardial infarction, atorvastatin treatment decreased the apoptosis of myocardial cells, suggesting the possible mechanism by which atorvastatin functions in protecting against heart failure.

Keywords: atorvastatin, heart failure, myocardial infarction, ER stress response, apoptosis.

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How to cite this article:
Song XJ, Yang CY, Liu B, Wei Q, Korkor MT, Liu JY, Yang P. Atorvastatin Inhibits Myocardial Cell Apoptosis in a Rat Model with Post-myocardial Infarction Heart Failure by Downregulating ER Stress Response. Int J Med Sci 2011; 8(7):564-572. doi:10.7150/ijms.8.564. Available from http://www.medsci.org/v08p0564.htm