All-trans-retinoic acid attenuates neointima formation with acceleration of reendothelialization in balloon-injured rat aorta

ABSTRACT

Retinoic acids may inhibit vascular smooth muscle cell proliferation, but may promote endothelial cell proliferation in cell culture. However, little data are available about the effects of all-trans-retinoic acid (ATRA) on endothelial regeneration and functional recovery in an experimental model of vascular injury. Accordingly, we investigated whether ATRA may attenuate neointima formation and accelerate endothelial regeneration with functional recovery in balloon-injured rat aorta. Twelve-week-old male Sprague-Dawley rats underwent endothelial denudation of the thoracic aorta by balloon injury. Fourteen rats were fed a standard rat pellet diet. Another 14 rats were fed ATRA (1.5 mg/day) for 2 weeks. The animals were killed on day 14 for organ chamber study and morphometric analysis. Rats in the ATRA group had a significantly improved acetylcholine-induced relaxation response than those in control group. However, endothelial independent response was not significantly different between the two groups. The extent of reendothelialization was markedly superior in the ATRA group compared with control group (p>0.05). Furthermore, neointima area and the ratio of neointima to medial area were significantly less in ATRA group than in control group (p>0.05). In conclusion, ATRA may accelerate endothelial regeneration with functional recovery, and attenuate neointima formation in balloon-injured rat aorta.