| Objective To investigate the influnce of all-trans retinoic acid (ATRA) on the process of luminal narrowing, the phenotypic modulation and proliferation of vascular smooth muscle cell(VSMC) and the expression of cyclin dependent kinase inhibitor P21cipl,P27kipl in rats artery after aortic balloon withdrawal injury. To disclose the mechanisms by which ATRA prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) .Methods 54 SD rats were randomly divided into 3 groups.Group l(n=6)served as controls and were killed 28 days after procedure.Group 2(operation group n=24)and Group 3 (ATRA group n=24) had balloon induced endothelium denudation at thoracic aorta and were killed at 2,7,14,28 days after artery injury .All rats were predosed with ATRA(30mg.kg-l.d-l) or corn oil by gavage 4 days before injury and continued to each indicated time . After the thoracic aorta were harvested ,we used immunohistochemistry staining to measure the protein expression of SM-a-actin, PCNA,cyclin dependent kinase inhibitor P21and P27 . Meanwhile vessel morphological measurement was taken.Results (1)In operation group,there were distinct neointima formation(14d: 0.150 0.030 28d: 0.173 0.030) and narrow luminal area at day 14 and day 28(28d: 1.641 0.088 vs 2.043 0.108, P<0.01). (2)Histomorphometry revealed ATRA-mediated decrease in neointima area (14d: 0.057 0.017 vs 0.150 0.030 28d: 0.075 0.017 vs 0.173 0.030, P<0.01) and intimal/medial area ratio (0.31H0.050 vs 0.139 0.035, PO.01) as well as significant increase in luminal area (1.901 0.085 vs 1.641 0.088, P<0.0),larger internal elastic lamina area (1.976 0.078 vs 1.813 0.065, PO.01 ) and larger external elastic lamina area (2.516 0.081 vs 2.360 0.072, P<0.01) at day 28. ㊣n normal rat arteries SM-a-actin was expressed abundantly; after balloon injury, the expression of SM-a-actin was downregulated significantly and reached the lowest at day 2 and then trended toward the normal level; in tunica intima , SM-a-actin could be measured notable at day Hand 28 . In normal rat arteries no PCNA was expressed; after balloon injury, the expression of PCNA increased obviously and reached the peak at day 2 and then trended toward the normal level; in tunica intima , VSMC proliferated extremely at day 7 and then decreased. In normal rat arteries P21 was not detected; after ballooninjury, P21 can be detected at day 14 and 28. In normal rat arteries P27 was detected; after balloon injury,P27 expression in media decreased ,reached the lowest level at day 2 and then upregulated ;in neointima , P27 could be detected at day 14 and 28. (4)In ATRA -treated group SM-α-actin was upregulated in both media and neointima while the cell proliferation was decreased significantly (P<0.01). (5)Less PCNA immunostaining were found in the ATRA group than in operation group (P<0.01). (6)In ATRA -treated group P21 was already present in the neointima at day 7 and strongly expressed at day 14 and 28 while the VSMC proliferation was decreased significantly(P<0.01). ㊣n ATRA-treated group P27 downregulation was inhibited in media and P27 was already present in the neointima at day 7 and strongly expressed at day 14 and 28 while the proliferation of VSMC was decreased significantly(P<0.01). (8)The expression of SM-a-actin, P21,P27 and the cell proliferation(PCNA) were in remarkable negative correlation(P<0.01).Conclusion (1)There were distinct neointima formation and luminal area lossin rats artery after aortic balloon withdrawal injury; (2)After balloon withdraw injury, expression of PCNA in VSMC increased while expression of SM-α-actin and P27 decreased greatly and P21 can be detected at day 14 and 28; (3)ATRA inhibited the downregulation of SM-α-actin and P27 and induced the expression of SM-a-actin , P21 , P27 significantly in injured artery, meanwhile the expression of PCNA was inhibited greatly at all indicated time; (4)ATRA attenuated neointima formation and luminal stenosis distinctly; (5)Inhibiting the progress of cell cycle and proliferation of VSMC by maintaining and inducing th...
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