Shear stress induces angiotensin converting enzyme expression in cultured smooth muscle cells: possible involvement of bFGF.

Abstract:

OBJECTIVE:Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. METHODS:Rat aortic endothelial cells, smooth muscle cells and fibroblasts isolated from Wistar rats were submitted to shear stress using a laminar shear flow parallel chamber. RESULTS:A 10 dynes/cm2 shear rate for 24 h increased ACE activity in the three vascular cell types (x 2.14 in endothelial cells, x 2.9 in smooth muscle cells, x 3.33 in fibroblasts). This induction was blocked by a 24 h pre-incubation with a translation blocker (10(-4)M cycloheximide) showing the role of protein neosynthesis. Therefore the study was focused on smooth muscle cells and we demonstrated that the increase in ACE activity was due to an elevation in ACE mRNA level in response to a 10 dynes/cm2 shear stress for 24 h. This induction was dependent on the shear intensity (P < 0.0001). Six hours of a 15 dynes/cm2 shear stress showed no effect on ACE activity or mRNA expression. In contrast, the same duration of shear significantly increased bFGF mRNA level (x 3.7). Conversely, bFGF dose dependently increased ACE mRNA expression and activity in smooth muscle cells. This result suggests that bFGF could be one of the potential inductors of ACE expression in the stressed smooth muscle cells. CONCLUSIONS:Mechanical stress increases ACE expression in vascular cells. bFGF could be one of the potential factors involved in this activation. This phenomenon could participate in the role of ACE activity in vascular wall remodeling.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Gosgnach W,Challah M,Coulet F,Michel JB,Battle T

doi

10.1016/s0008-6363(99)00269-2

subject

Has Abstract

pub_date

2000-01-14 00:00:00

pages

486-92

issue

2

eissn

0008-6363

issn

1755-3245

pii

S0008-6363(99)00269-2

journal_volume

45

pub_type

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