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.