title: Angiotensin-II induces phosphorylation of ERK1/2 and promotes aortic adventitial fibroblasts differentiating into myofibroblasts during aortic dissection formation.
abstract: The development of acute aortic dissection (AD) is attributed to unbearable wall tension superimposed on disordered of cells and extracellular matrix (ECM) in the aortic wall. Adventitial fibroblasts (AFs) phenotypic differentiation response to stress exhibits essential function to regulate the remolding of vascular. Little is known about the AFs phenotypic differentiation and its possible mechanism in patients with AD. In this study, we examined their roles in AD. Surgical specimens of the aorta from AD patients (n = 10) and controls (n = 10) were tested for α-smooth muscle actin (α-SMA), extracellular signal-regulated kinase 1,2 (ERK1/2) and phospho-ERK1/2 expression, respectively by western blot. When compared with controls, protein levels of α-SMA was significantly decreased and levels of phospho-ERK1/2 was increased significantly in the aortic wall from patients with AD. Immunohistochemistry results showed elevated staining of both α-SMA and phospho-ERK1/2 in the adventitia of the aortic wall from patients with AD, on the contrary, staining of α-SMA in the media was decreased compared with controls. In vitro, the Raf/MEK/ERK pathway was involved in Ang-II-induced phenotypic differentiation and matrix metalloproteinase-2 (MMP-2) mRNA expression in AFs. This study provides a new insight into the biological action of AFs and phospho-ERK1/2 promoting phenotypic differentiation and MMP-2 expression, suggesting an important role of AFs in leading to disorder the delicate balance of ECM metabolism in the aortic wall, so that AFs may be an essential participant during AD formation.
authors.affiliation: Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, #99 Ziyang Road, Wuhan, 430060, Hubei, China, wangzhiwp@gmail.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Zongli
authors.initials: Z
authors.lastname: Ren
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000804:Angiotensin II; D048052:Mitogen-Activated Protein Kinase 3