Arterial injury repair in nonhuman primates-the role of PDGF receptor-beta.
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.


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.


CONCLUSIONS
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.
Englesbe
Michael J
MJ
Department of Surgery, Division of Vascular Surgery, University of Washington Medical Center, Seattle, Washington, USA. englesbe@med.umich.edu
Davies
Mark G
MG
Hawkins
Suzanne M
SM
Hsieh
Patrick C H
PC
Daum
Günter
G
Kenagy
Richard D
RD
Clowes
Alexander W
AW
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000494:pharmacology; D001158:Arteries / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D007866:Leg / Q000098:blood supply*; D008297:Male; D010215:Papio; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing; D014947:Wounds and Injuries / Q000209:etiology
D000906:Antibodies; D020797:Receptor, Platelet-Derived Growth Factor beta