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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:400.)
© 2002 American Heart Association, Inc.

Vascular Biology

Increased Plasmin and Serine Proteinase Activity During Flow-Induced Intimal Atrophy in Baboon PTFE Grafts

Richard D. Kenagy; Jens W. Fischer; Mark G. Davies; Scott A. Berceli; Suzanne M. Hawkins; Thomas N. Wight; Alexander W. Clowes

From the Division of Vascular Surgery, Department of Surgery (R.D.K., M.G.D., S.A.B., S.M.H., A.W.C.) and Pathology (J.W.F., T.N.W.), University of Washington, Seattle.

Address correspondence to Richard Kenagy, PhD, Department of Surgery, Box 356410, University of Washington, School of Medicine, 1959 NE Pacific St, Seattle, WA 98195-6410. E-mail rkenagy{at}u.washington.edu

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.

Key Words: intimal atrophy • flow • plasminogen • urokinase • proteoglycan • smooth muscle cells

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