EFFECTS OF ALL-TRANS-RETINOIC ACID ON NEOINTIMA FORMATION AND EXPRESSION OF PCNA AFTER VASCULAR BALLOON INJURY

Objective To investigate the effects of all-trans retinoic acid(atRA) on neointima formation and expression of proliferating cell nuclear antigen(PCNA) after vascular balloon injury to determine whether atRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and its mechanisms. Methods The rats were randomly divided into sham-operated group, injury group, and atRA group. The aortic tissue was taken on day 2, 7, and 14, respectively. Morphometric ana- lysis and immunohistochemistry for PCNA were performed at different times. Results Histomorphometry revealed atRA-mediated reductions in neointima area and intimal/medial area ratio by day 7 and 14 ( t=3.96,-6.98;P 0.01), and significant increases in luminal area by day 14 ( t=3.98,P 0.01). Immunohistochemical analysis revealed expression of PCNA within the media of injured thoracic arteries at 48 hours. At day 7, expression of these markers declined to basal levels in the media but was detected within the intimal lesion. By day 14, when a prominent intimal lesion formed, they were largely confined to the luminal surface. Less PCNA immunostaining were found in the atRA group than in the control group( t=7.20-15.39,P 0.01). Conclusion atRA may inhibit the VSMC cell cycle by reducing the over-expression of PCNA,inhibit intimal hyperplasia and prevent restenosis.