ROLE OF ENDOGENOUS CARBON MONOXIDE IN NEOINTIMAL FORMATION INDUCED BY BALLOON-INJURY IN RAT AORTA

OBJECTIVE: The present study investigated the role of endogenous carbon monoxide (CO) in the pathogenesis of neointimal formation induced by balloon injury in rat. METHOD: Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter. DNA, collagen and elastin contents of each intima-media were estimated; and heme oxygenase (HO) activity and CO production in vascular smooth muscle cell (VSMC) were measured after administration of HO inhibitor. RESULT: Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury, and at the same time HO activity and CO production in VSMC were markedly increased. Administration of HO inhibitor, zinc deuteroporphyrin 2,4-bisglycol (ZnDPBG), could effectively inhibit HO activity and CO production, significantly enhance neointimal formation (aortic intima/media ratio were 21.4+/-1.8% vs 17.6+/-2.0%, P<0.05 on day 7; and 30.5+/-2.4% vs 23.0+/-2.2%, P<0.01 on day 21, respectively, compared with balloon alone group). CONCLUSION: We concluded that 1) inhibition of CO production may enhance neointimal formation induced by endothelial denudation, implying endogenous CO play an protective role in response to vascular injury, and 2) induction of HO activity may be applied clinically for preventing restenosis after angioplasty.