Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

Abstract

Fluid shear stress has been shown to be an important regulator of vascular structure and function through its effect on the endothelial cell. We have explored the effect of shear stress on the expression of the heparin-binding growth factors platelet-derived growth factor B chain (PDGF-B) and basic fibroblast growth factor (bFGF) in bovine aortic endothelial cells using a purpose-built cone-plate viscometer. Using morphometric analysis, we have mimicked the endothelial cell shape changes encountered in vivo in response to shear stress and correlated these with changes in gene expression. Steady laminar shear stress of 15 and 36 dyn/cm2 both resulted in endothelial cell shape change, but the higher shear stress induced greater and more uniform alignment in the direction of flow and nuclear protrusion after 24 h. Steady laminar shear stress of both 15 and 36 dyn/cm2 induced a significant 3.9-and 4.2-fold decrease, respectively, in PDGF-B mRNA at 9 h. In contrast, steady laminar shear of 15 dyn/cm2 induced a mild and transient 1.5-fold increase in bFGF mRNA while shear of 36 dyn/ cm2 induced a significant 4.8-fold increase at 6 h of shear which remained at 2.9-fold at 9 h. Pulsatile and turbulent shear stress showed the same effect as steady laminar shear stress (all at 15 dyn/cm2 time-average magnitude) on PDGF-B and bFGF mRNA content. Cyclic stretch (20% strain, 20/min) of cells grown on silicone substrate did not significantly affect either PDGF-B or bFGF mRNA levels. These results suggest that expression of each peptide growth factor gene is differentially regulated by fluid shear stress in the vascular endothelial cell. These results may have implications on vascular structure and function in response to hemodynamic forces and present a model for the study of transduction of mechanical stimuli into altered gene expression. (J. Clin.

Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells

“…The modulation is mediated in part by the regulation of genes encoding for many proteins including vasoactive substances, growth factors and protooncogenes [15,33,47,60], affecting cell structure and function in endothelium [21,48]. Recent studies have shown that shear stress affected the brain endothelial cell surface [20,43,70].…”

Experimental and theoretical modelling of blind-ended vessels within a developing angiogenic plexus

“…Within vessels containing both an inlet and outlet, shear forces on the endothelial cells are key regulators of vascular segment survival (Meeson, 1996;Azmi and O'Shea, 1984). Low flow rates in EC cultures have been shown to result in alterations in the distribution of cytoskeletal proteins (Dardik, 2005) and morphology (Malek, 1993) and induction of tissue factor expression, the cell surface initiator protein for the haemostatic cascade. In addition, cultures exposed to physiologically low rates of flow yield gene expression profiles similar to endothelium from atherosclerotic-prone arteries (e.g.…”

Fluid Shear Stress Reduces 11β-Hydroxysteroid Dehydrogenase Type 2

“…The ss activates a number of intracellular signals, such as de novo transcription of growth factors (platelet-derived growth factor, transforming growth factor-␤) 46,47 or vasoconstrictors such as endothelin. 48 Integrins, which are mechanosensors of ss, prompt tyrosine kinase-related intracellular signals 49 ; however, several conditions have to be fulfilled for signaling: integrin aggregation, integrin presence, tyrosine kinase activity with phosphorylation of FAK, and actin cytoskeletal integrity, with the latter 2 addressed in this study.…”