Shear stress-induced shedding of soluble intercellular adhesion molecule-1 from saphenous vein endothelium

Abstract

Within 6 h, shear stress upregulated intercellular adhesion molecule-1 (ICAM-1) (two- to four-fold, P<0.001) and induced matrix metalloproteinase-2 (MMP-2) in cultured human saphenous vein endothelial cells. By 8 h endothelial ICAM-1 levels returned to baseline, with concomitant increase in soluble ICAM-1 (sICAM-1) ( P<0.001) and MMP-9 had been induced. Inclusion of a hydroxamate metalloproteinase inhibitor partially reversed the effects on ICAM-1 and sICAM-1 at 8 h, whereas TIMP-1, -2 or -3 had no effect. MMP-9, but not MMP-2, co-immunoprecipitated with ICAM-1. sICAM-1 was processed distal to Arg441, indicating that MMP-9, docking to ICAM-1, contributes to sICAM-1 shedding and attenuation of the shear stress-induced upregulation of ICAM-1.