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

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.

• Authors: Michael J Englesbe, Mark G Davies, Suzanne M Hawkins, Patrick C H Hsieh, Günter Daum, Richard D Kenagy, Alexander W Clowes
• Journal: The Journal of surgical research (J Surg Res) Vol. 119 Issue 1 Pg. 80-4 (Jun 01 2004) ISSN: 0022-4804 [Print] United States
• PMID: 15126086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Animals
• Antibodies (blood, pharmacology)
• Arteries (injuries, pathology, physiopathology)
• Catheterization (adverse effects)
• Cell Division (drug effects)
• Leg (blood supply)
• Male
• Papio
• Receptor, Platelet-Derived Growth Factor beta (antagonists & inhibitors, metabolism)
• Tunica Intima (drug effects, pathology)
• Tunica Media (drug effects, pathology)
• Wound Healing
• Wounds and Injuries (etiology)