Shear stress-induced shedding of soluble intercellular adhesion molecule-1 from saphenous vein endothelium.
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.
Sultan
Sabena
S
Department of Vascular Surgery (Charing Cross site), Imperial College London, St Dunstan's Road, London W6 8RP, UK.
Gosling
Martin
M
Nagase
Hideaki
H
Powell
Janet T
JT
D004730:Endothelium, Vascular / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012501:Saphenous Vein / Q000166:cytology*; D012995:Solubility; D013314:Stress, Mechanical; D015854:Up-Regulation
D018799:Intercellular Adhesion Molecule-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9