Shear stress magnitude and directionality modulate growth factor gene expression in preconditioned vascular endothelial cells

Abstract

Objective: The purpose of this study was to simultaneously monitor the transcriptional levels of 12 endothelial growth factor genes in response to alterations in wall shear stress (WSS) under conditions relevant to the development of intimal hyperplasia, a major cause of arterial bypass graft failure. Methods: Human umbilical vein endothelial cells were preconditioned in vitro under steady flow (WSS, 15 dynes/cm2) for 24 hours before being subjected to WSS at 25 (Δ = +10), 15 (Δ = 0), 5 (Δ = -10), 2.5 (Δ = -12.5), and 0 (Δ = -15) dynes/cm2 or low magnitude WSS reversal (-2.5 dynes/cm2) for 6 hours. A focused complementary DNA array was used to simultaneously measure messenger RNA expression levels for END1, endothelial nitric oxide synthase (NOS3), platelet-derived growth factor A, platelet-derived growth factor B (PDGFB), acidic fibroblast growth factor, basic fibroblast growth factor, transforming growth factor-α, transforming growth factor-β, vascular endothelial growth factor, insulin-like growth factor-1, epidermal growth factor, and angiotensin converting enzyme. Results: Preconditioning significantly (P