Effect of perindopril on endoplasmic reticulum stress-related protein GRP78 and caspase-12 in rats with myocardial infarction

Objective To investigate whether the effect of perindopril on ameliorating heart function is associated with inhibiting endoplasmic reticulum stress (ERS) signaling pathway. Methods Myocardial infarction (MI) models in male SD rats were reproduced by ligation of the left anterior descending coronary artery (LAD). Rats that survived post-MI within 24h were randomly divided into model group (n=8) and perindopril group (n=8). Eight sham-operated rats were used as controls which underwent the same surgical procedure except that the suture around the coronary artery was not tied. The rats in peridopril group were treated with peridopril in a dose of 2mg/(kg.d) for 4 weeks. The rats in model group and sham group received an equal amount of saline. At the end of 4 weeks, transthoracic echocardiogram was performed to measure the ventricular morphology and heart function, including left ventricular end systolic diameter (LVESD) and end diastolic diameter (LVEDD), as well as left ventricular ejection fraction (LVEF) and fraction shortening (FS). The expression levels of GRP78 and caspase-12 protein were assessed with immunohistochemistry or Western blotting. Results Compared with the sham-operated group, the LVEDD and LVESD significantly increased after 4 weeks of MI, while the EF and FS decreased in model group. Perindopril significantly inhibited ventricular hypertrophy and improved heart function (P<0.05). Western blotting or immunohistochemistry showed that the important endoplasmic reticulum stress markers, GRP78 and caspase-12 significantly increased in perindopril treated rats after MI, showing that perindopril significantly attenuated these changes. Conclusion Perindopril may improve the heart function, which may be partly related to a decrease in the expression level of GRP78 and caspase-12, and by blocking ERS signaling pathway.\n\t\t\n\t\tDOI: 10.11855/j.issn.0577-7402.2014.01.01