Effects Of ATRA On Intimal Proliferation And Expression Of PCNA, P16 And PDGF-BB After Thoracic Aorta Balloon Injury In Rats

Objective To investigate the effects of all-trans retinoic acid(ATRA) on intimalproliferation , expression of proliferation cell nuclear antigen(PCNA) p16 and Platelet derived growth factor-BB(PDGF-BB) after vascular injury in rats,to determine whether ATRA can prevent restenosis after percutaneous transluminal coronary angioplasty(PTCA) and the mechanisms.Methods Make models of aortic endothelial denudation of rats by balloncatheter. Rats were randomly allocated into three groups;.Group l(n=24) were given vascular balloon injury.Group 2 (n=24) were given ATRA(30mg.kg-1d-1)into stomach from 4 days before injury to 28 days after injury . Group3(n=6)served as contrals were killed at 14 days after operation. The thoracic tissues were calculated morphologically at day7.14,28 after injury.The expression of PCNA P16 and PDGF-BB were measured by means of immunohistochemical technique and imagine analyzer.Results (1) In operation group(7d,14d and 28d),there were distinct intimaproliferation and luminal area decrease.(2)Histomorphometry revealed ATRA-mediated reduction in neointima area (0.0475 + 0.0091 versus 0.0703 + 0.0135, P< 0.05) and intimal/medial area ratio(0.0878 + 0.0206 versus 0.2650 + 0.0565,P< 0.05) but no difference between luminal area( 1.8668 + 0.0943 versus 1.7903+0.1024,P> 0.05) by 7 days, ATRA-mediated reduction in neointima area(0.0571 + 0.0150 versus 0.1451 + 0.0324,P< 0.01;0.0747 + 0.0167 versus 0.1728 + 0.0301 ),intimal/medial area ratio(0.1084 +0.0326 versus 0.2650+0.0565,P< 0.01;0.1067+0.0346 versus 0.2837 + 0.0501,P< 0.01)as well assignificant increases in luminal area(1.9134+0.1106 versus 1.6908 + 0.1129,P< 0.01;1.9012 +0.0848 versus 1.6405 + 0.0878,P< 0.01) by 14,28days.(3) Immunohistochmical analysis revealed expression of PCNA within the media of injured thoracic arteries at 2 days time point..At 7days time points,expression of PCNA declinedto basal levels in the media but was detected within the intimal lesion.By 14,28 days.when a prominent intimal lesion was formed,they are largely confined to the luminal surface.When given ATRA,the expression of PCNA decreased at every time point(in media at 2days, 12.1643 + 1.5722vs24.0168 + 1.9890,P< 0.01;at 7days 4.6229 + 0.9471vs9.8436+ 1.8201,P< 0.01;in intima at 7days 16.8393 + 1.1083vs35.6759 + 3.2795,P< 0.01 ;at 14days 8.7584+0.8373vs21.9235+2.6280,P< 0.01) (4)In operation group,the expression changes of p16 was inappearnt at every time point.When given ATRA, the expression of P16 begun increasing at 2 days and reached maximum at day 14 after vascular balloon injury(8.8711 + 1.7182 versus 17.5652+1.3261,P< 0.01;9.0121 + 1.6322 versus 22.0942 +3.0691,P< 0.0I;8.5321 + 1.5462 versus 15.2132+1.6591,P< 0.01).(5) In operation group ,the positive expression of PDGF-BB were found at day 2 after balloon injury and reached maximum at day 14. When given ATRA , the index of PDGF-BB expression reduced(l 13.1912 + 37.5321 versus 176.0212 + 34.8721,P< 0.01:145.3212 + 54.1821 versus 356.7112 + 78.6521 ,P< 0.01;186.8912+65.0321 versus 611.4012 +95.9821 ,P< 0.01 ;95.6312 +28.7221 versus 182.6812 +35.7421 ,P< 0.01).Conclusion (1) Neointimal priliferation and luminal area decrease occurred inballoon injured thoracic in rats.(2)Expression of PCNA and PDGF-B in VSMCs increased, but that of P16 is inapperant after balloon injury.(3)Given ATRA the expression of PCNA and PDGF-B in VSMCs decreased, but that of P16 increased, (4)ATRA can effectively repress intima proliferation after vascular injury,which may be associated with inhibiting the proliferation of vascular smooth muscle cells through down regulating the expression of PCNA,PDGF-BB and up regulating the expression of P16.