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(Circulation. 1999;99:564-569.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
PDGFß Receptor Blockade Inhibits Intimal Hyperplasia in the Baboon
From ZymoGenetics, Seattle, Wash (C.E.H., D.G.); the Division of Vascular Surgery, University of Utah, Salt Lake City (L.W.K.); the Department of Surgery, University of Washington, Seattle (S.V., R.K., A.W.C.); BioDevelopment, Bellevue, Wash (T.K.); Wyeth-Ayerst Research, Princeton, NJ (D.L.C.); and Celltech Therapeutics, Slough, UK (S.Y., H.F., G.Y.).
Correspondence to Charles E. Hart, ZymoGenetics, Inc, 1201 Eastlake Ave E, Seattle, WA 98102. E-mail Hartc{at}zgi.com
Background—We have evaluated the use of a mouse/human chimeric anti–platelet-derived growth factor-ß receptor antibody in combination with heparin to inhibit intimal hyperplasia in the saphenous artery of the baboon after balloon angioplasty.
Methods and Results—The study evaluated lesion development in sequential injuries made 28 days apart. Each animal received control treatment after the first injury and antibody/heparin therapy after the second injury to the contralateral artery. The antibody was administered by bolus intravenous injections (10 mg/kg) on study days 1, 4, 8, 15, and 22 and heparin coadministered by continuous intravenous infusion at a dose of 0.13 mg/kg per hour. Morphometric analysis of tissue sections showed a 53% decrease in intimal area after antibody/heparin treatment (P=0.005), corresponding to a 40% decrease in the intima-to-media ratio (P=0.005). Smooth muscle cell proliferation in the injured wall, measured at both 4 and 29 days after balloon injury, were similar in the control and antibody/heparin-treated animals.
Conclusions—These data suggest that platelet-derived growth factor plays a key role in the development of intimal lesions at sites of acute vascular injury in the nonhuman primate.
Key Words: restenosis • angioplasty • balloon • receptors • antibodies • platelet-derived factors
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