title: 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.
authors.affiliation: *Department of Cardiology, Tangdu Hospital, Xi'an, China; †Department of Cardiology, Fifth Hospital of PLA, Yinchuan, China; and ‡Department of Physiology, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Niu
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xue
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Lianyou
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis / Q000517:prevention & control; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D001127:Arginine Vasopressin; D003094:Collagen; D000803:Angiotensin I; D019703:Calcineurin; C118790:angiotensin I (1-7)