| Background and Objectives:Percutaneous coronary intervention (PCI) is an important procedure for the treatment of coronary stenosis. However, restenosis or reocclusion after balloon injury remains a serious problem. The major cause of restenosis is neointimal hyperplasia, which results from an excessive proliferative response of vascular smooth muscle cells (VSMCs) to numerous cytokines coursed by mechanical injury. This proliferative process includes VSMCs activation, migration from media to intima, and proliferation in intima. There is a great deal of evidence to show the process of VSMCs growth involves oxidative stress and inflammation related to the accumulation of leukocytes and platelets. Since platelets are thought to play an important part in the proliferation of VSMCs by releasing the growth factors, antiplatet drus have often been used clinically. However, the effects of these drugs on restenosis in clinical fields are still controversial. But among these drugs ,cilostazol ,a phosphodiesterase type 3 (PDE3) inhibitor, is proved to be useful for preventing restenosis in clinical situations.It increase the concentration of cyclic AMP(cAMP) by selectively blocking PDE3, resulting in the inhibition of platelet aggregation. As cilostazol is also know to suppress the growth of VSMCs in vitro and in vivo, the molecular mechanisms by which cilostazol prevent restenosis however are still unknown.Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a new class of oxidized LDL receptors, is a membrane protein that is expressed in the endothelial cells, smooth muscle cells, macrophages, and platelets. The expression of LOX-1 is markedly increased by cytokines and oxidative stress, such as tumor necrosis factor-α(TNF-α) and reactive oxygen species (ROS). LOX-1 is a multiligand receptor .Ligand binding to LOX-1 induces superoxide generation. This is followed by the activation of transcription factors and the induction of the expression of adhesion molecules and chemokines. There is a great deal of evidence to show that LOX-1 has played an important role in the atherogenesis and the pathogenesis of atherosclerotic plaque rupture and inflammatory intramyocardial vasculopathy. Resently, The LOX-1 expression has been reported to significantly increase in the neointima after balloon injury in various animal models of neointimal hyperplasia, such as rats and rabbits. Hinagata et al reported neointimal hyperplasia after balloon injury was markedly attenuated by treatment with anti–LOX-1 antibody in a rat model. These findings suggest that LOX-1 expressed in the neointima is involved in the pathogenesis of restenosis after arterial injury, and, therefore, LOX-1 is an important molecular mechanism of neointimal hyperplasia after arterial injury and may be a potential therapeutic target for the prevention/treatment of restenosis.In this study, we focused on the expression of LOX-1 after balloon arterial injury in a rat model and the effect of cilostazol on the expression of LOX-1 and production of ROS. Thus we studied whether cilostazol inhibis neointimal formation after balloon injury and inhibit the expression of LOX-1 and production of ROS in rats model。Methods:Forty male SPF Sprague-Dawley(SD)rats selected were randomly divided into five groups: shan-operation group(group A,n=8),24thh model group(group B, n=8),7thd model group(group C, n=8),14thd model group(group D, n=8) and cilostazol group (group E, n=8).rats in group B,C,D,E were performed left common carotid artery balloon injury. Rats in group E were given cilostazol 20mg/(kg.d) three weeks before operation one week.For all the rats ,peripheral blood were taken .and Malondialdehyde (MDA) were detected with Thibabituric Acid (TBA).The left common carotid arteries were obtained to detect the expression of LOX-1 mRNA and protein by semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry ,respectively. The histopathology of the arteries was examined after by hematoxylin/eosin(HE ) staining .Image analysis system was applied to measure the area of intimal and neointimal(IA),the area of media(MA) and the ratio of IA/MA was obtained .With SPSS13.0 statiatical software, carry out statiatics analysis, Significance was set at P<0.05. Results(1) Neointimal hyperplasia after balloon arterial injury in a rat model can be observed in group C,D,E. Compared with group D ,the ratio of IA/MA in group C,E was significantly lower(P<0.05) .(2) The level of serum MDA increased significantly in group B,C,D,E. Compared with group D, the level of serum MDA decreased significantly in group E(P<0.05).(3) There was the expression of LOX-1mRNA and protein in neointimal hyperplasia after balloon arterial injury in a rat model except shan-operation group.The expression level of LOX-1 was significantly lower in the cilostazol group than that in group D (P<0.05),Conclusion1,Cilostazol can inhibit carotid artery intimal proliferation and delay a significant progression of restenosis.2,LOX-1 is highly expressed in neointimal hyperplasia after balloon arterial injury in a rat model , cilostazol can significantly inhibit expression of LOX-1mRNA and protein.3,The level of serum MDA increased significantly after balloon arterial injury in a rat model, cilostazol can significantly decrease the level of serum MDA.4,Cilostazol can significantly inhibit intimal proliferation by depressing the expression level of LOX-1 and serum MDA.
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