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Effects of angiotensin-(1-7) on the proliferation and collagen synthesis of arginine vasopressin-stimulated rat cardiac fibroblasts: role of mas receptor-calcineurin-NF-κB signaling pathway.

Abstract：

:: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(1-7) [Ang-(1-7)] was reported to be beneficial for cardiac remodeling by its antifibrotic effect. To evaluate the effect of Ang-(1-7) on AVP-stimulated CFs and the subsequent signaling molecules involved, CFs isolated from neonatal rat hearts were incubated with AVP and treated with or without Ang-(1-7). Cell proliferation, cell cycle, collagen production, and related cellular signaling molecules were then assessed. The results showed that Ang-(1-7) dose-dependently inhibited cell proliferation and collagen production in AVP-stimulated CFs. In addition, Ang-(1-7) also significantly suppressed calcineurin activity in a dose-dependent manner in AVP-stimulated CFs, which was associated with reduced collagen production. Accordingly, the nuclear translocation and transcriptional activity of nuclear factor-kappa B (NF-κB), downstream signal of calcineurin, were also notably restrained by Ang-(1-7) in AVP-stimulated CFs. Furthermore, the inhibitory effect of Ang-(1-7) on AVP-activated calcineurin-NF-κB signaling was completely reversed by the Mas receptor antagonist A-799. These findings suggest that Ang-(1-7) exerts an antifibrotic effect by inhibiting AVP-stimulated CF proliferation and collagen synthesis by inactivating Mas receptor-calcineurin-NF-κB signaling pathway.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Niu X,Xue Y,Li X,He Y,Zhao X,Xu M,Zhao L

doi

10.1097/FJC.0000000000000151

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

536-42

issue

eissn

0160-2446

issn

1533-4023

pii

00005344-201412000-00007

journal_volume

pub_type

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Effects of angiotensin-(1-7) on the proliferation and collagen synthesis of arginine vasopressin-stimulated rat cardiac fibroblasts: role of mas receptor-calcineurin-NF-κB signaling pathway.