Effect Of All-trans Retinoic Acid (atRA) On Proliferation Of Vascular Smooth Muscle Cells And The Expression Of E2F1,AKT1 In Carotid Atherosclerosis In Rabbits

Objective To investigate the influence of all-trans retinoic acid (atRA) on intimal proliferation and the expression of E2F1 and AKTl in endothelial injured carotid in rabbits and its mechanisms.Methods 36 New Zealand rabbits were randomly divided into 6 groups: sham-operation groups (A,B), operation groups (A,B), treatment groups (A,B). There were 6 rabbits in each group. The rabbits in the treatment groups and the operation groups were fed with high cholesterol chow and subject to the carotid endothelial injury by air desiccation after 2 weeks. The sham-operation groups were fed with conventional chow, underwent surgery without endothelium injury. atRA was administered daily to the treatment groups by gavages. The rabbits in the A groups and B groups were sacrificed respectively at 7 and 28 days after surgery. The carotid artery segments were harvested for histomorphometry observation. Immunohistochemistry were used to detect E2F1,AKTland PCNA protein.Results In operation groups, the E2F1,AKT1and PCNA expression were significantly up regulated, neointimal formation was found in carotid artery at 7 days after injury and severe intima thickness,atherosclerosis was found at 28 days after injury. In the treatment group, the intimal area, intimal/medial area ratio and maximum plague thickness of the artery at 28 days after surgery were lower than the operation group, (P<0.01; P<0.001; P<0.01), the expression of E2F1,AKT1and PCNA were lower too(P<0.01, P<0.01, P<0.05 respectively).Conclusion The results indicate that atRA can suppress the proliferation of vascular smooth muscle cells, inhibit neointima and atherosclerosis progression in endothelium injured artery. This may relevant to that atRA can suppress the E2F1 and AKT1 expression.