Increased plasmin and serine proteinase activity during flow-induced intimal atrophy in baboon PTFE grafts

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Abstract

High blood flow causes intimal atrophy and loss of extracellular matrix in PTFE aortoiliac grafts. We have investigated whether matrix-degrading proteinases are altered in this baboon model of atrophy using zymography, western analysis, and a versican degradation assay. After four days of high flow, urokinase was increased and plasminogen activator inhibitor-1 was decreased in the intima. Plasminogen was increased after seven days. Pro-matrix metalloproteinase (MMP)-2, activated MMP-2, and proMMP-9 levels were modestly increased by high flow at 7 days, whereas MMP-3 and tissue inhibitor of metalloproteinases-1 were not altered. Extracts of 4-day high-flow intimas degraded more 35S-methionine-labeled versican than low-flow intimal extracts, and this activity was inhibited by AEBSF, a serine proteinase inhibitor, and a plasmin antibody. In contrast, this activity was not inhibited by the MMP inhibitor, BB-94 (Batimastat). These data suggest that serine proteinases, including plasmin, may be largely responsible for extracellular matrix degradation in this primate model of flow-induced intimal atrophy.

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CITATION STYLE

APA

Kenagy, R. D., Fischer, J. W., Davies, M. G., Berceli, S. A., Hawkins, S. M., Wight, T. N., & Clowes, A. W. (2002). Increased plasmin and serine proteinase activity during flow-induced intimal atrophy in baboon PTFE grafts. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(3), 400–404. https://doi.org/10.1161/hq0302.105376

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