Arterial injury repair in nonhuman primates—the role of PDGF receptor-β

• Published in: The Journal of surgical research 2004-06, Vol.119 (1), p.80-84
• Main Authors: Englesbe, Michael J, Davies, Mark G, Hawkins, Suzanne M, Hsieh, Patrick C.H, Daum, Günter, Kenagy, Richard D, Clowes, Alexander W
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - blood; Antibodies - pharmacology; arterial injury; Arteries - injuries; Arteries - pathology; Arteries - physiopathology; Biological and medical sciences; Catheterization - adverse effects; Cell Division - drug effects; General aspects; intimal hyperplasia; Leg - blood supply; Male; Medical sciences; nonhuman primate; Papio; PDGFR-β; Receptor, Platelet-Derived Growth Factor beta - antagonists & inhibitors; Receptor, Platelet-Derived Growth Factor beta - metabolism; Tunica Intima - drug effects; Tunica Intima - pathology; Tunica Media - drug effects; Tunica Media - pathology; vascular injury; Wound Healing; Wounds and Injuries - etiology
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2003.10.015

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-β. Fundamental differences with the well-characterized rat arterial injury model have been found. Thirty-eight baboons received a unilateral balloon injury to the saphenous artery and were treated with a chimeric blocking antibody to PDGFR-β or vehicle control for 7, 14, or 28 days. The arteries were evaluated morphologically and for cell proliferation. 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-β 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-β completely inhibited both intimal and medial growth at 14 days, but there was less of an effect on intimal growth at 28 days. Blockade of PDGFR-β may be a clinical approach to inhibit intimal hyperplasia in humans, but this study raises concerns about the long-term efficacy of this treatment.