Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR-1-dependent pathway.
Animals
Cell Hypoxia
/ drug effects
Cell Line
Cell Survival
/ drug effects
Connexin 43
/ metabolism
KCNQ1 Potassium Channel
/ metabolism
Male
MicroRNAs
/ genetics
Myocardial Infarction
/ drug therapy
Myocardial Reperfusion Injury
/ drug therapy
Myocytes, Cardiac
/ cytology
Proto-Oncogene Proteins c-bcl-2
/ metabolism
Rats
Rats, Sprague-Dawley
Telmisartan
/ administration & dosage
Bcl-2
KCNQ1
connexin 43
hypoxic H9c2 cells
miR-1
myocardial ischaemia/reperfusion
telmisartan
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
05
04
2019
revised:
27
05
2019
accepted:
24
06
2019
pubmed:
2
8
2019
medline:
26
9
2020
entrez:
2
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31369209
doi: 10.1111/jcmm.14534
pmc: PMC6787508
doi:
Substances chimiques
Connexin 43
0
Gja1 protein, rat
0
KCNQ1 Potassium Channel
0
Kcnq1 protein, rat
0
MIRN1 microRNA, rat
0
MicroRNAs
0
Proto-Oncogene Proteins c-bcl-2
0
Telmisartan
U5SYW473RQ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6635-6645Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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