Retinoic acid suppresses intimal hyperplasia and prevents vessel remodeling following arterial injury

Vitamin A and its derivatives (retinoids) are capable of inhibiting vascular smooth muscle cell proliferation in vitro. The present study examines the effect of two retinoids, all-trans retinoic acid and 13-cis retinoic acid, on intimal hyperplasia following arterial injury. After receiving varying doses of all-trans retinoic acid or 13-cis retinoic acid, 78 male Sprague-Dawley rats underwent standard balloon catheter denudation of the left common carotid artery. Morphometric analysis and immunohistochemistry for proliferating cell nuclear antigen was performed at early and late time points. Intimal/medial ratios were reduced in a dose-dependent fashion for animals treated with all-trans retinoic acid (P = 0.001) and 13-cis retinoic acid (P = 0.004). Proliferating eel nuclear antigen labeling indices were reduced after treatment with all-trans retinoic acid and 13-cis retinoic acid at early time points post-injury. At a dose of 10 mg/kg, both all-trans retinoic acid and 13-cis retinoic acid inhibited vessel remodeling as measured by increases in luminal diameter (P < 0.05) and external elastic lamina (P < 0.05). Retinoids are an attractive clinical option for the treatment of restenosis following angioplasty and arterial surgery. (C) 1999 The International Society for Cardiovascular Surgery, Published by Elsevier Science Ltd. All rights reserved.