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

Objective: Hemodynamic stresses are considered to be important regulators o f gene expression in vascular cells. In this study, we have investigated th e role of shear stress on ACE expression in cultured rat vascular cells, an d focused on the regulation of ACE expression in smooth muscle cells. Metho ds: Rat aortic endothelial cells, smooth muscle cells and fibroblasts isola ted from Wistar rats were submitted to shear stress using a laminar shear f low parallel chamber. Results: A 10 dynes/cm(2) sheer rate for 24 h increas ed ACE activity in the three vascular cell types (x 2.14 in endothelial cel ls, x 2.9 in smooth muscle cells, x 3.33 in fibroblasts). This induction wa s blocked by a 24 h pre-incubation with a translation blocker (10(-4)M cycl oheximide) showing the role of protein neosynthesis. Therefore the study wa s focused on smooth muscle cells and we demonstrated that the increase in A CE activity was due to an elevation in ACE mRNA level in response to a 10 d ynes/cm(2) shear stress for 24 h. This induction was dependent on the shear intensity (P<0.0001). Six hours of a 15 dynes/cm(2) shear stress showed no effect on ACE activity or mRNA expression. In contrast, the same duration of shear significantly increased bFGF mRNA level (x3.7). Conversely, bFGF d ose dependently increased ACE mRNA expression and activity in smooth muscle cells. This result suggests that bFGF could be one of the potential induct ors of ACE expression in the stressed smooth muscle cells. Conclusions: Mec hanical stress increases ACE expression in vascular cells. bFGF could be on e of the potential factors involved in this activation. This phenomenon cou ld participate in the role of ACE activity in vascular wall remodeling. (C) 2000 Elsevier Science B.V. All rights reserved.