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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:89.)
© 2000 American Heart Association, Inc.

Vascular Biology

All-trans-Retinoic Acid Limits Restenosis After Balloon Angioplasty in the Focally Atherosclerotic Rabbit

A Favorable Effect on Vessel Remodeling

Peter J. Wiegman; William L. Barry; John A. McPherson; Coleen A. McNamara; Lawrence W. Gimple; John M. Sanders; Gregory G. Bishop; Eric R. Powers; Michael Ragosta; Gary K. Owens; Ian J. Sarembock

From the Cardiovascular Division, Department of Medicine (P.J.W., W.L.B., J.A.M. C.A.M., L.W.G., J.MS, G.G.B., E.R.P., M.R., I.J.S.) and the Department of Molecular Physiology and Cellular Biophysics (G.K.O.), University of Virginia Health Sciences Center, Charlottesville.

Correspondence to Ian J. Sarembock, MD, Cardiovascular Division, Department of Medicine, Box 158, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail ijs4s{at}virginia.edu

Abstract—All-trans-retinoic acid (atRA) has potent in vitro effects on a number of processes involved in vascular injury and repair, such as modulating smooth muscle cell (SMC) proliferation and inducing SMC differentiation, and may play an important role in the in vivo response to vascular injury. We hypothesized that atRA would limit restenosis after balloon angioplasty through SMC-modulated changes in plaque size and vessel geometry. Balloon angioplasty was performed on rabbits with focal femoral atherosclerosis randomized to treatment with atRA or saline. At 28 days after balloon angioplasty, minimal luminal diameter was significantly larger in the atRA group (1.24±0.17 versus 1.12±0.22 mm, P=0.02). Histomorphometry confirmed a larger lumen area (0.51±0.20 versus 0.34±0.13 mm², P=0.004) in the atRA group, with no difference in absolute plaque area. Internal elastic lamina and external elastic lamina areas were significantly larger in the atRA group (0.89±0.27 versus 0.66±0.24 mm², P=0.001, and 1.29±0.38 versus 0.98±0.32 mm², P=0.001, respectively). Vessel sections exhibited significantly more -actin and desmin immunostaining (P=0.01) in the atRA-treated group. No differences in early cellular proliferation and collagen content were detected with the use of bromodeoxyuridine. In this atherosclerotic model of vascular injury, atRA limits restenosis after balloon angioplasty by effects secondary to overall vessel segment enlargement at the angioplasty site rather than by effects on plaque size or cellular proliferation. Increased -actin and desmin immunostaining suggest a possible role for phenotypic modulation of SMCs in this favorable remodeling effect.

Key Words: retinoic acid • restenosis • remodeling • angioplasty • smooth muscle cells

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