Regulation of extracellular matrix production and degradation of endothelial cells by shear stress

摘要

Extracellular matrix (ECM) including subendothelial basement membranes developed more in the anti-atheroscleiotic regions, which were exposed to laminar shear stress, than in the atheiosclerotic-prone regions, which were exposed to turbulent low mean shear stiess. Here we present evidence that the laminar shear stress influence the subendothelial ECM formation through the regulation of endothelial collagen metabolism Methods: Confluent endothelial cells (EC) obtained from bovine aorta or human umbilical veins were exposed to laminar shear stress using parallel-plate flow chamber:After exposure, collagenase-sensitive products labeled with 3H-proline in both media and cells were measured as collagenous protein, and analyzed by fluorography. Expression of matrix metalloproteinase 2 (MMP2), which degrades type IV collagen in basement membrane, in EC was analyzed by gelatin zymography, Western blotting and Northern blotting Results: (1) Over 90% of collagenous protein produced by EC was collagen type IV (2) Collagen synthesis of EC was increased by shear stiess time-dependently, (3). The MMP2 secretion from EC into medium was interrupted completely by shear stiess, although the levels of intracellular protein and mRNA expression of MMP2 were unchanged. (4) Albumin changed MMP2 secretion from EC Conclusion: Oui data suggest that laminar shear stiess contribute to the formation of anti-atherosclerotic micioenvironment in vessel through the regulation of collagen type IV metabolism of EC.