Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress.
The endoplasmic reticulum (ER) stress-induced apoptotic pathway is associated with the development of acute myocardial infarction (AMI). Cortistatin (CST) is a novel bioactive peptide that inhibits apoptosis-related injury. Therefore, we investigated the cardioprotective effects and potential mechanisms of CST in a rat model of AMI.
Male Wistar rats were randomly divided into sham, AMI, and AMI + CST groups. Cardiac function and the degree of infarction were evaluated by echocardiography, cardiac troponin I activity, and 2,3,5-triphenyl-2H-tetrazolium chloride staining after 7 days. The expression of CST, ER stress markers, and apoptotic markers was examined using immunohistochemistry and Western blotting.
Compared to the AMI group, the AMI + CST group exhibited markedly better cardiac function and a lower degree of infarction. Electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that myocardial apoptosis occurred after AMI. Cortistatin treatment reduced the expression of caspase 3, cleaved caspase 3, and Bax (proapoptotic proteins) and promoted the expression of Bcl-2 (antiapoptotic protein). In addition, the reduced expression of glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding proteins homologous protein, and caspase 12 indicated that ER stress and the apoptotic pathway associated with ER stress were suppressed.
Exogenous CST has a notable cardioprotective effect after AMI in a rat model in that it improves cardiac function by suppressing ER stress and myocardial apoptosis.
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Zhi-Yu
ZY
Shi
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Yue
Y
Liu
2 Department of Pathology, The Second Hospital of Harbin, Harbin, Heilongjiang, China.
Li
L
Dong
3 Department of Cardiology, Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Bo
B
Zhang
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Meng
M
Zhao
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Wen-Xiu
WX
Liu
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Xin
X
Zhang
1 Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Xin-Hua
XH
Yin
acute myocardial infarction; cortistatin; endoplasmic reticulum stress; myocardial apoptosis