| Objective To investigate the effects of all-trans Retinoic Acid(ATRA) on neointima formation and expression of proliferating cell nuclear antigen (PCNA) and Matrix metalloproteinases(MMPs) after vascular balloon injury, to determine whether ATRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and the mechanisms.Methods The rats were randomly divided into three groups: non-injuryed group(n=6); control group(n=24); ATRA group(n=24),control group rats were inserted 2F homemade catheter to the abdominal aorta, with 0.1ml saliline dilated balloon.withdrawed balloon to the common carotid artery, repeated 6 times. Then extracted the catheter, sutured the incision, balloon injury did not give non-injuried group rats. ATRA group rats were given ATRA(30mg kg-1 d-1 PO) from 4 days before injury to the day been killed after injury.The aortic tissues were taken at 48h, 7d, 14d and 28d. Morphometric analysis and immunohistochemistry for PCNA,MMP2 and MMP9 were performed at different time points.Results (1)In control group(7, 14days and 28days) ,there were distinct intima proliferation and luminal area decreases. (2)Histomorphometry revealed ATRA-mediated reductions in neointima area (0.0475 + 0.0091 versus 0.0703 + 0.0135, P<0.05) and intimal/medial area ratio (0.0895 + 0.0206 vs 0.1330 + 0.0565, P<0.05) but no differences in luminal area(1.8668 + 0.0943 versus 1.7903 + 0.1024, P > 0.05) by 7 days, ATRA-mediated reductions in neointima area (0.0571 +0.0150 versus 0.1451 +0.0324, 0.0747 + 0.0167 vs 0.1728 + 0.0301, p<0.01) , intimal/medial area ratio (0.1068 + 0.0326 vs 0.2650+0.0565, 0.1067+0.0346 vs 0.3104+0.050l,P<0.01) as well as significant increases in luminal area (1.9134 + 0.1106 vs 1.6908 + 0.1129, 1.9012 + 0.0848 vs 1.6405 +0.0878, p<0.01) by 14 days and 28 days. (3)Immunohistochemical analysis revealed that PCNA,MMP2 expression appear within the media of injured thoracic arteries at 48 hours . At 7days, expression of these markers declined to basal levels in the media but was detected within the intimal lesion . By 14 days, when a prominent intimal lesion was formed, they were largely confined to the luminalsurface,then began to decline,still detected at 28d. The expression of MMP-9 increased significantly in the media of vessel at 2d after injury,then became little after 7d (4)Less MMP2 immunostaining were found in the ATRA group than in the control group(7d,21.4105+ 2.6231 vs 28.2723 +2.8903; 14d, 17.5121 + 1.0834 vs 22.2815 + 2.3505,P<0.01) .Less MMP9 immunostaining were found in the ATRA group than in the control group(48h,7.2311 + 0.6431 vs 9.7604 + 0.9340, P<0.01). (5) Less PCNA immunostaining were found in the ATRA group than in control group (media 48h 12.1643 + 1.5722 vs 24.168 +1.9890, P<0.01, media 7d 4.6229 + 0.9471 vs 9.8436 + 1.8201, P<0.01, intima 7d 16.8393 + 1.1083 vs 35.6759 + 3.2795, P<0.01 and intima 14d 8.7584 + 0.8373 vs 21.9235+2.6280, P<0.01, intima 28d 2.0933 + 0.3096 vs 3.0562 + 0.5817,P<0.05 .respectively).Conclusion (1) Neointima proliferation and luminal area decreases occurred in balloon-injured aorta. (2) Expression of MMP2, MMP9 and PCNA in VSMC increased after balloon withdraw injury. (3)ATRA inhibited the over-expression of MMP2 , MMP9 and PCNA. (4) ATRA attenuated neointima formation and luminal stenosis distinctly. (5) ATRA may inhitit the over-expression of MMP2 MMP9 and PCNA,then decrease proliferation and migration of VSMC, which could prevent the occurrence of restenosis.
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