© 2000 American Heart Association, Inc.
Molecular Medicine |
Heparin Blockade of Thrombin-Induced Smooth Muscle Cell Migration Involves Inhibition of Epidermal Growth Factor (EGF) Receptor Transactivation by Heparin-Binding EGF-Like Growth Factor
Presented in part at the Experimental Biology ‘99 meeting, Washington DC, April 17–21, 1999, and published in abstract form (FASEB J. 1999;13:A35, A136).
From the Department of Surgery (A.K., B.R.V., G.D., A.W.C.), University of Washington (Seattle); and Scios Inc (J.A.A.), Sunnyvale, Calif.
Correspondence to Andreas Kalmes, PhD, University of Washington School of Medicine, Department of Surgery, Box 356410, 1959 NE Pacific St, Seattle, WA 98195-6410. E-mail kalmes{at}u.washington.edu
Abstract—Agonists of G protein–coupled receptors, such as thrombin, act in part by transactivating the epidermal growth factor (EGF) receptor (EGFR). Although at first a ligand-independent mechanism for EGFR transactivation was postulated, it has recently been shown that this transactivation by various G protein–coupled receptor agonists can involve heparin-binding EGF-like growth factor (HB-EGF). Because thrombin stimulation of vascular smooth muscle cell migration is blocked by heparin and because heparin can displace HB-EGF, we investigated the possibility that thrombin stimulation of smooth muscle cells (SMCs) depends on EGFR activation by HB-EGF. In rat SMCs, EGFR phosphorylation and extracellular signal-regulated kinase (ERK) activation in response to thrombin are inhibited not only by the EGFR inhibitor AG1478 and by EGFR blocking antibody but also by heparin and by neutralizing HB-EGF antibody. HB-EGF–dependent signaling induced by thrombin is inhibited by batimastat, which suggests a requirement for pro-HB-EGF shedding by a metalloproteinase. We further demonstrate that this novel pathway is required for the migration of rat and baboon SMCs in response to thrombin. We conclude from these data that the inhibitory effect of heparin on SMC migration induced by thrombin relies, at least in part, on a blockade of HB-EGF–mediated EGFR transactivation. (Circ Res. 2000;87:92-98.)
Key Words: heparin • growth factors • muscle, smooth • migration
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|
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|
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|
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 |
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