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J Cell Mol Med. 2019 Aug 1. doi: 10.1111/jcmm.14534. [Epub ahead of print]

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR-1-dependent pathway.

Author information

1
Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
2
Department of Mental and Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
3
Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy.
4
Multidisciplinary Department of Surgical and Dental Specialties, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Abstract

The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA-1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague-Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real-time polymerase chain reaction showed that expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and the protein Bcl-2 were significantly increased by telmisartan in the reperfused myocardium, paralleled by microRNA-1 down-regulation. In vitro, the transfection of cardiomyocytes with microRNA-1 reduced the expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2 in the cells. Telmisartan (50 µmol/L) 60 minutes before hypoxia/reoxygenation, while not affecting the levels of miR-1 in transfected cells in normoxic condition, almost abolished the increment of miR-1 induced by the hypoxia/reoxygenation to transfected cells. All together, telmisartan cardioprotected against the myocardial damage through the microRNA-1 modulation, and consequent modifications of its downstream target connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2.

KEYWORDS:

Bcl-2; KCNQ1; connexin 43; hypoxic H9c2 cells; miR-1; myocardial ischaemia/reperfusion; telmisartan

PMID:
31369209
DOI:
10.1111/jcmm.14534
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