Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression

Heiko Methe, Mercedes Balcells, Maria Del Carmen Alegret, Marina Santacana, Blanca Molins, Anne Hamik, Mukesh K. Jain, Elazer R. Edelman

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Resum

Endothelial cell phenotypes markedly differ, depending upon function and vascular bed of origin. Differences might account for specific susceptibility to pathological conditions. As leukocyte adhesion to activated endothelium is the initiating event in a range of diseases, we compared the influence of vascular bed-specific flow patterns on adhesion molecule expression in human saphenous vein (HSVEC) and coronary artery endothelial cells (HCAEC). In vitro, immune cell attachment was increased 1.6-fold when tumor necrosis factor (TNF)-α-stimulated HSVEC were exposed to coronary artery flow in place of physiological venous flow and 1.9-fold higher compared with attachment to cytokine-stimulated HCAEC exposed to coronary artery flow. This was associated with increased concentrations of soluble E-selectin, VCAM-1, and ICAM-1 in supernatants of HSVEC exposed to coronary artery flow compared with HCAEC exposed to the same flow pattern. Venous and coronary artery flow both increased TNF-α-induced E-selectin and ICAM-1 expression on HSVEC, but only coronary artery flow increased VCAM-1 expression. In marked contrast to HSVEC, venous and coronary artery flow attenuated TNF-α-induced E-selectin and VCAM-1 expression on HCAEC, whereas coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With the exception of cytokine-induced ICAM-1, adhesion molecule expression on HSVEC exposed to coronary artery flow exceeded expression on HCAEC. Thus ICAM-1 expression involves complex flow-dependent and -independent pathways with marked dissimilarities between the two endothelial cell types studied. Interestingly, Kruppel-like factor (KLF) 4 overexpression in HCAEC and HSVEC significantly reduced TNF-α-induced E-selectin and VCAM-1 expression in static conditions, while ICAM-1 expression remained constant. Furthermore, both flow patterns induced KLF2 and KLF4 expression in HCAEC and HSVEC. Venous and coronary artery flow differentially influence endothelial adhesion molecule and transcription factor expression, depending on the vascular bed of origin. Differences in adhesion molecule expression and subsequent immune cell adhesion between HSVEC and HCAEC may contribute to different susceptibility to pathological conditions.

Idioma originalAnglès
Pàgines (de-a)H2167-H2175
RevistaAmerican Journal of Physiology - Heart and Circulatory Physiology
Volum292
Número5
DOIs
Estat de la publicacióPublicada - de maig 2007

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