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(Circulation. 2005;112:587-591.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Biliverdin Administration Prevents the Formation of Intimal Hyperplasia Induced by Vascular Injury

Atsunori Nakao, MD; Noriko Murase, MD; Chien Ho, PhD; Hideyoshi Toyokawa, MD; Timothy R. Billiar, MD; Shinichi Kanno, MD

From the Thomas E. Starzl Transplantation Institute (A.N., N.M., H.T.) and Department of Surgery (T.R.B., S.K.), University of Pittsburgh, Pittsburgh, Pa, and the NMR Center, Carnegie Mellon University (C.H.), Pittsburgh, Pa.

Correspondence to Shinichi Kanno, MD, Department of Surgery, University of Pittsburgh, School of Medicine, W1554, Biomedical Science Tower, 200 Lothrop St, Pittsburgh, PA 15213. E-mail shk34{at}pitt.edu

Received September 27, 2004; revision received March 29, 2005; accepted April 12, 2005.

Background— Autologous vein grafts and balloon angioplasty are still commonly used for arterial reconstructive procedures. Their success is limited by the development of intimal hyperplasia (IH). Biliverdin (BVD), one of the by-products of heme degradation, has been shown to have potent antioxidant and antiinflammatory effects. We hypothesized that BVD administration would protect vascular tissue against vascular injury.

Methods and Results— The effects of BVD administration against IH after vascular injury were analyzed in an arterialized vein graft model and a balloon injury model in rats. BVD treatment significantly suppressed the development of IH in both models compared with those without BVD. The mechanisms by which BVD treatment inhibits IH development might include decreasing c-Jun NH₂ terminal kinase activation and preventing apoptosis of endothelial cells. BVD also suppressed vascular smooth muscle cell migration in vitro.

Conclusions— BVD administration prevented IH associated with arterialized vein graft vasculopathy or balloon angioplasty-induced vessel injury. These results suggest that a treatment regimen with exogenous BVD administration could provide an effective therapeutic adjunct to facilitate transfer of experimental treatments for vascular injury to the clinic.

Key Words: angioplasty • antioxidants • apoptosis • reperfusion • restenosis

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