Regulation of Yes-Associated Protein by Laminar Flow.

Annals of Vascular Surgery
G ChitragariBauer E Sumpio

Abstract

The cells lining the endothelium of blood vessels are recognized as playing critical roles in vascular health and disease. The mechanisms that regulate endothelial cells (ECs) proliferation and release of mediators remain poorly understood but represent a potential source of disease modulation. Actin-cytoskeleton remodeling and cell shape have been suggested as key regulators of phosphorylation of yes-associated protein (YAP) which controls cellular growth and proliferation. Because different types of flow have been shown to affect cell shape and cytoskeleton differently, we hypothesized that the level of phosphorylated yes-associated protein (pYAP; serine 127) decreases in EC exposed to pulsatile uniform flow or steady laminar flow, whereas exposure to pulsatile disturbed flow causes an increase or no change. Human umbilical vein endothelial cells (HUVECs) were exposed to pulsatile uniform flow, pulsatile disturbed flow, or steady laminar flow and analyzed by immunoblotting. Exposure of HUVECs to steady laminar flow caused a significant decrease in the levels of pYAP (69.7 + 2.6%, P < 0.05), whereas total YAP levels remained nearly unchanged. Conversely, exposure to either pulsatile uniform or disturbed flow caused a significa...Continue Reading

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