Effects Of All-Trans Retinoic Acid On Intimal Proliferation And VEGF, VCAM-1 Expression In Endothelium Injured Carotid Artery In Rabbits

Objective To observe the effects of all-trans retinoic acid(atRA) on intimal proliferation,the expression of vascular endothelial growth factor(VEGF),vascular cell adhesion molecule-1 (VCAM-1) and proliferating cell nuclear antigen(PCNA) in rabbit carotid arteries after endothelium injured.Methods 36 New Zealand rabbits were randomly divided into 6 groups:treatment groups(A,B), control groups(A,B),sham-operation groups(A,B).The rabbits in the treatment groups and the control groups were fed with high cholesterol chow and subject to carotid endothelial injury by air desiccation.The sham-operation groups were underwent surgery without endothelium injury.AtRA was administered daily to the treatment groups by gavages.Rabbits in the A groups and B groups were respectively sacrificed at 7 and 28 days after surgery.The carotid artery segments were harvested for histomorphometry observation.Immunohistochemistry was used to detect VEGF,VCAM-1 and PCNA.Results In the sham-operation groups,the artery cavosurface is smooth,without atherosclerosis and VCAM-1,PCNA expression found.Neointimal proliferation was found at 7 days after surgery in the control group.Intimal hyperplasia,atheromatous plaque and vascular stenosis was found at 28 days,the expression of VEGF,PCNA and VCAM-1 was remarkably upregulated.In the treatment groups,the pathological changes were lighter,the intimal area at 28 days was lower than that of the control group(0.15±0.04 mm~2 versus 0.37±0.10 mm~2,t=4.770,P<0.001),the expression of VEGF and VCAM-1 was significantly lower too(t=3.280～3.703,P<0.01),the PCNA expression decreased both at 7 and 28 days(t=5.251～4.926,P< 0.001).Conclusion AtRA reduces neointimal proliferation and atherosclerosis progression in endothelium injured artery,the mechanism may be related to inhibition of the expression of VEGF and VCAM-1.