Transgenic overexpression of transient receptor potential vanilloid subtype 1 attenuates isoproterenol-induced myocardial fibrosis in mice.
Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel with high permeability to Ca2+. Intracellular Ca2+ signaling is an essential regulator of endothelial nitric oxide (NO) synthase (eNOS) that plays a beneficial role in myocardial fibrosis. The aim of the present study was to determine the role of TRPV1 in isoproterenol-induced myocardial fibrosis. Transgenic mice overexpressing TRPV1 were generated on a C57BL/6J genetic background. An animal model of myocardial fibrosis was created by subcutaneously injecting the mice with isoproterenol. We found that the wild-type mice exhibited a significant increase in heart/body weight ratio, left ventricle/body weight ratio, left ventricular end-diastolic pressure (LVEDP), the cardiac fibrotic lesion area and collagen content, as well as a marked decrease in eNOS phosphorylation and NO/cyclic guanosine monophosphate (cGMP) levels at 2 weeks after the administration of isoproterenol (all p<0.01). However, these changes were significantly attenuated in the TRPV1 transgenic mice (p<0.05 or p<0.01). Moreover, the beneficial effects on myocardial fibrosis exerted by the overexpression of TRPV1 were attenuated by the administration of the eNOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) (all p<0.05). Similar anti-fibrotic effects were observed in in vitro experiments with primary cultured cardiac fibroblasts. The findings of our study suggest that TRPV1 overexpression attenuates isoproterenol‑induced myocardial fibrosis.
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Qiang
Q
Wang
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Yunrong
Y
Zhang
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
De
D
Li
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Yan
Y
Zhang
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Bing
B
Tang
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Gang
G
Li
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Yongjian
Y
Yang
Department of Cardiology, Chengdu Military General Hospital, Jinniu, Chengdu, Sichuan 610083, P.R. China.
Dachun
D
Yang
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006439:Hemodynamics; D007545:Isoproterenol; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism*; D016276:Ventricular Function
D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP; D007545:Isoproterenol