Cyclic stretch induces the expression of vascular endothelial growth factor in vascular smooth muscle cells

Abstract

Objective: Accumulating evidence links the release of vascular endothelial growth factor (VEGF) by vascular smooth muscle cells (VSMC) to normal endothelial cell (EC) function, repair and maintenance. Using an in vitro model we investigate the role of cyclic stretch on both the release of VEGF by VSMC and the phosphorylation of a VEGF receptor on EC. Methods: Bovine VSMC and EC were exposed to 10% cyclic strain for 4 hours. VEGF mRNA steady-state levels of VSMC were analysed by northern blot hybridisation. The presence of secreted VEGF from VSMC was determined by assaying the migration of EC. VEGF receptor phosphorylation on stretched EC was assayed by immunoblotting. Results: The steady-state level of VEGF mRNA in stretched VSMC increased 3.3 (± 0.6) fold above that of unstretched VSMC (p<0.005). Migration of EC was stimulated 8.3 (± 1.1) and 14.6 (± 1.3) fold by media from unstretched and stretched VSMC respectively, demonstrating a 1.8 fold increase due to stretch alone (p<0.05). Cyclic stretch resulted in phosphorylation of the VEGF receptor KDR. Conclusion: Exposure of VSMC to physiological levels of stretch induces a biologically significant increase in VEGF secretion and may provide an arterial stimulus for maintenance of steady state levels of VEGF essential for EC survival.