title: Atorvastatin ameliorates myocardial ischemia/reperfusion injury through attenuation of endoplasmic reticulum stress-induced apoptosis.
abstract: Endoplasmic reticulum stress (ERS) is known to play an important role in mediating myocardial ischemic/reperfusion (I/R) injury. Some previous studies have shown that atorvastatin alleviates myocardial I/R injury in animal models, but whether attenuation of ERS-induced apoptosis contributes to this effect remains to be elucidated. Therefore, in this study, we sought to investigate the modulatory effect of atorvastatin on myocardial I/R-induced ERS in rats. Myocardial I/R injury was induced in rats by occlusion of the left anterior descending coronary artery (LAD) for 0.5 h followed by 2 h of reperfusion. Atorvastatin was administered at different dosages (10 mg/kg, 20 mg/kg, and 40 mg/kg) at the onset of reperfusion. The levels of the CK-MB and LDH were detected by ELISA. Myocardial ischemia and infarct size were evaluated by Evans blue and tetrazolium chloride (TTC) staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to investigate myocardial cell apoptosis. The expression levels of the genes encoding glucose-regulated protein-78 (GRP78, widely used as a marker of ERS), C/EBP homologous protein (CHOP) and caspase-12 (widely used as markers of ERS-induced apoptosis) were assessed using RT-PCR. The expression levels of the ERS proteins GRP78, CHOP, caspase-12, c-Jun NH2 terminal kinase (JNK) and phosphorylated JNK (p-JNK) were detected by western blot. Our results showed that atorvastatin treatment (20 mg/kg and 40 mg/kg) significantly reduced myocardial infarct size and myocardial cell apoptosis, and decreased the plasma levels of CK-MB and LDH in I/R rats. This treatment also significantly modulated mRNA and protein levels, specifically down-regulating GRP78, CHOP and caspase-12 expression along with JNK activation. These results suggest that the attenuation of ERS-induced apoptosis may be involved in the cardioprotective mechanisms of atorvastatin in myocardial I/R injury.
authors: Department of Cardiology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China.
authors: Hui
authors: H
authors: Wu
authors: Department of Cardiology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, China.
authors: Qizhu
authors: Q
authors: Tang
authors: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University Yichang 443003, Hubei Province, China.
authors: Jun
authors: J
authors: Yang
authors: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University Yichang 443003, Hubei Province, China.
authors: Jiawang
authors: J
authors: Ding
authors: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University Yichang 443003, Hubei Province, China.
authors: Ming
authors: M
authors: Ye
authors: Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University Yichang 443003, Hubei Province, China.
authors: Wusong
authors: W
authors: Dong
keywords: Atorvastatin; apoptosis; endoplasmic reticulum stress; ischemia reperfusion injury