Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats

Wenjia Chen; Juan Liang; Yu Fu; Yuanyuan Jin; Runan Yan; Jinyu Chi; Wenxiu Liu; Yue Liu; Xinhua Yin

doi:10.21037/atm.2020.02.93

Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats

Ann Transl Med. 2020 Mar;8(6):309. doi: 10.21037/atm.2020.02.93.

Authors

Wenjia Chen¹, Juan Liang², Yu Fu¹, Yuanyuan Jin¹, Runan Yan¹, Jinyu Chi¹, Wenxiu Liu¹, Yue Liu¹, Xinhua Yin¹

Affiliations

¹ Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
² Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.

Abstract

Background: The present study was designed to examine whether cortistatin (CORT) could protect rats from myocardial injury induced by subcutaneously injecting isoproterenol (ISO) and to clarify the possible mechanisms.

Methods: Male Sprague-Dawley (SD) rats were placed at random into four groups: the control group, the ISO group, the ISO + CORT 25 µg/(kg·d) group, and the ISO + CORT 50 µg/(kg·d) group. Rat models of myocardial injury were established with the subcutaneous (s.c.) injections of 85 mg/kg ISO for 2 days. In the ISO+ CORT 25 µg/(kg·d) group and ISO+ CORT 50 µg/(kg·d) group, rats were given s.c. injections of CORT 25 µg/(kg·d) and CORT 50 µg/(kg·d) on the day before ISO, 3 days, respectively. Serum malondialdehyde (MDA) content, lactate dehydrogenase (LDH) activity, and creatine kinase isoenzyme (CK-MB) activity were measured by corresponding test kits. Western blot was applied to evaluate the expression of endoplasmic reticulum stress-related protein glucose regulatory protein 78 (GRP78), enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate specific proteinase-12 (caspase-12), LC3-II, Beclin-1, and p62 in the rat myocardium.

Results: CORT alleviated the increased enzyme activities of serum LDH and CK-MB, and content of MDA (a typical marker of lipid peroxidation) in rats induced by ISO. CORT also prevented pathological myocardial injury in rats induced by ISO. Moreover, CORT attenuated the increased protein levels of GRP78, CHOP, and caspase-12, and reduced the increase of LC3-II, LC3-II/I, Beclin-1, and p62 in rats induced by ISO.

Conclusions: These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. This supports CORT as a potentially being a new target for preventing and treating myocardial injury and its related disease.

Keywords: Cortistatin (CORT); acute myocardial injury; autophagy; endoplasmic reticulum stress.