Effects Of All-trans Retinoic Acid On Neointimal Formation And Expression Of Cyclins,C-myc Protein In The Rat Thoracic Aorta After Balloon Withdrawal Injury

Objective To investigate the process of neointimal formation and expression of proliferating cell nuclear antigen (PCNA), CyclinD|> CyclinE s C-myc protein in the rat thoracic aorta and the effects of all-trans Retinoic Acid(ATRA) on them after balloon withdrawal injury. To determine whether ATRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and the mechanisms.Methods Make the endothelial denuded rat thoracic aorta model by balloon withdrawal injury (BWI). The rats were randomly allocated into three groups .Group1 (n=6): non-injuried group; Group2(n=24) were dosed orally with ATRA(30mg kg-1 d-1) 4 days before BWI and up to 28 days after injury. Group 3 (n=24) were given BWI and dosed orally with an equivalent volume (0.5ml) sesame oil 4 days before BWI and continued for additional 28 days. Observe the expression of the PCNA and the CyclinD1 CyclinE C-myc protein in the injured vascular wall by immunohistochemistry at day 2,7,14,28 after injury. Analysize the change of morphology by the computer-based image analysis system at different time points.Results (1) In control group : the migration and proliferation of VSMC had existed at day 2 after BWI. The thickening of intima had begun at day 7 after injury, and they were more significant at day 14. The proliferation of VSMC decreased at day 28,but extracellular matrix increased and the intimal thickning continued. (2)The express of PCNA and CyclinD1, CyclinE C-myc protein increased significantly at day 2 after injury and began to decrease at day 14. (3) The neointima area and the ratio of neointima to media area were significantly less in ATRA group than in control group. ATRA-mediated reductions in neointima area (0.057 + 0.017 vs 0.150 + 0.030, P<0.01) , intimal/medial area ratio (0.107 + 0.035 vs 0.274 + 0.050, P<0.01) by 14 days. ATRA-mediated reductions in neointima area (0.075 + 0.017 vs 0.173 + 0.030, P<0.01) , intimal/medial area ratio (0.140+0.036 vs 0.284+0.050, P<0.01) as well as significant increases in luminal area (1.901 +0.085 vs 1.640+0.088, P<0.01) by 28 days.(4)ATRA alsocan reduce the positive index of PCNA and CyclinD1 CyclinE . C-myc protein.Conclusion (1)Neointima proliferation and luminal area decreases occurred in balloon-injured aorta.(2)The expression of PCNA and CyclinD1, CyclinE , C-myc protein increased in the process of intimal thickening after BWI. (3) ATRA could inhibit the proliferation of the VSMC and attenuated neointima formation and luminal stenosis in the artery after balloon injury.(4)ATRA could inhibit the expression of PCNA, CyclinD1, CyclinE, C-myc protein in the artery after BWI. (5)To interfere the progress of cell cycle may be one of the mechanisms that ATRA can inhibit the restenosis after the operation of PCI.