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

Vitamin A and its derivatives (retinoids) are capable of inhibiting vascula r 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-D awley rats underwent standard balloon catheter denudation of the left commo n carotid artery. Morphometric analysis and immunohistochemistry for prolif erating cell nuclear antigen was performed at early and late time points. I ntimal/medial ratios were reduced in a dose-dependent fashion for animals t reated 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 ea rly 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 i ncreases in luminal diameter (P < 0.05) and external elastic lamina (P < 0. 05). Retinoids are an attractive clinical option for the treatment of reste nosis following angioplasty and arterial surgery. (C) 1999 The Internationa l Society for Cardiovascular Surgery, Published by Elsevier Science Ltd. Al l rights reserved.