Modulation of functional responses of endothelial cells linked to angiogenesis and inflammation by shear stress: differential effects of the mechanotransducer CD31

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Abstract

We investigated the roles of the 'mechanotransducer' CD31 in the effects of shear stress on endothelial gene expression and functional responses relevant to angiogenesis and inflammation. Human or murine endothelial cells (hEC or mEC) were exposed to different levels of shear stress, while expression of CD31 was modified using siRNA in the hEC, or mEC from CD31(-/-) mice. Quantitation of expression of genes linked to inflammation or angiogenesis showed several were sensitive to shear. In a 'wound' assay, exposure of EC to shear stress tended to align migration with the direction of flow and decrease the rate of closure compared to static cultures. When EC were cultured on filters, shear stress promoted migration away from the luminal surface. EC conditioned by shear stress recruited fewer flowing neutrophils, and showed reduced up regulation of E-selectin after stimulation with tumour necrosis factor-α (TNF). Use of siRNA against CD31 in the hEC, or testing of mEC from mice lacking CD31, indicated that expression of CD31 was not required for the shear-induced modification of wound closure. However, shear modulation of response to TNF was less effective in the absence of CD31, while reduction of CD31 reduced shear-sensitivity in some genes (e.g., eNOS), but not others (e.g., KLF-2). Thus, CD31 played a role in shear-sensitivity of some genes and of neutrophil recruitment, but not in modulation of endothelial migration. Different mechanotransducers may mediate different functional effects of shear stress. Hence, identification of the specific pathways may provide targets for therapeutic manipulation of angiogenesis or inflammation. J. Cell. Physiol. © 2011 Wiley-Liss, Inc.

Details

Original languageEnglish
Pages (from-to)2710-2721
Number of pages12
JournalJournal of Cellular Physiology
Volume227
Issue number6
Early online date24 Feb 2012
Publication statusPublished - Jun 2012