Arterial injury repair in nonhuman primates-the role of PDGF receptor-beta |
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Authors: | Englesbe Michael J Davies Mark G Hawkins Suzanne M Hsieh Patrick C H Daum Günter Kenagy Richard D Clowes Alexander W |
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Affiliation: | Department of Surgery, Division of Vascular Surgery, University of Washington Medical Center, Seattle, Washington, USA. englesbe@med.umich.edu |
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Abstract: | BACKGROUND: This study documents the time course of the response to injury of the saphenous artery in baboons and the role of the platelet-derived growth factor-beta. Fundamental differences with the well-characterized rat arterial injury model have been found. MATERIALS AND METHODS: Thirty-eight baboons received a unilateral balloon injury to the saphenous artery and were treated with a chimeric blocking antibody to PDGFR-beta or vehicle control for 7, 14, or 28 days. The arteries were evaluated morphologically and for cell proliferation. RESULTS: Both medial and intimal smooth muscle cell proliferation were elevated 7 days after injury and were back close to baseline at 14 days. Unlike the rat, blockade of PDGFR-beta inhibited medial proliferation over 80% at 7 and 14 days, while intimal proliferation was only inhibited at 14 days (>95%). Also, unlike the rat, the baboon arterial media, as well as the intima, increased in size by 14 days after injury. Blockade of PDGFR-beta completely inhibited both intimal and medial growth at 14 days, but there was less of an effect on intimal growth at 28 days. CONCLUSION: Blockade of PDGFR-beta may be a clinical approach to inhibit intimal hyperplasia in humans, but this study raises concerns about the long-term efficacy of this treatment. |
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Keywords: | arterial injury PDGFR-β vascular injury intimal hyperplasia nonhuman primate |
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