Fluid flow regulates E-selectin protein levels in human endothelial cells by inhibiting translation.

The purpose of this study was to determine the mechanism with which fluid flow inhibits endothelial E-selectin expression. Cultured human umbilical vein endothelial cells were stimulated with inflammatory agonists (tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta, oncostatin M, or phorbol ester) in the presence or absence of fluid flow (peak shear stress, approximately 12 dynes/cm(2)) imposed with an orbital shaker. E-selectin expression was assessed with ribonuclease protection assay, immunoblotting, enzyme-linked immunosorbent assay, or metabolic labeling as appropriate. All agonists caused human umbilical vein endothelial cells to express E-selectin protein. Fluid flow inhibited E-selectin protein levels by about 50% in response to TNF-alpha but had no effect on total E-selectin messenger RNA (mRNA) expression. Flow inhibited E-selectin protein production even after initiation of E-selectin transcription. Flow did not cause E-selectin to be shed from the cell surface nor was E-selectin degradation accelerated. Although fluid flow did not reduce total cellular E-selectin mRNA levels in response to TNF-alpha, the amount of E-selectin mRNA present in the actively translated polysome fraction was markedly attenuated. These findings indicate that E-selectin expression is subject to translational and transcriptional control. Fluid mechanical forces can regulate endothelial phenotype by targeting translational control points.

Citation

Larry W Kraiss, Neal M Alto, Dan A Dixon, Thomas M McIntyre, Andrew S Weyrich, Guy A Zimmerman. Fluid flow regulates E-selectin protein levels in human endothelial cells by inhibiting translation. Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 Jan;37(1):161-8

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PMID: 12514595

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