Effect Of Intensive Atorvastatin Therapy On B7-H3,B7–H4 In Peripheral Blood Monocytes Of Patients With Unstable Angina Undergoing Percutaneous Coronary Intervention

Background The main mechanism of the pathological pathogenesis of unstable angina pectoris(Unstable angina,UA)is changes of atherosclerotic plaque in coronary atherosclerosis secondary on the basis of internal instability,the local myocardial blood flow decreased significantly,such as intraplaque hemorrhage and plaque fibrous cap bleeding on the surface has cracks,platelet aggregation and coronary stimulation(or)artery spasm,leading to ischemia aggravated.Unstable angina pectoris of coronary heart disease is one of the common types,a large number of studies show that chronic inflammation throughout the process of atherosclerosis,inflammatory mediators activate effector cells produce inflammatory factors,which can affect the stability of the plaque fibrous cap promoted atherosclerosis plaque rupture and hemorrhage,finally lead to the formation of unstable plaque.B7-H3 and B7-H4 are new members of the B7 costimulatory molecule family in recent years.The new study confirmed that human and rat B7-H3 can effectively inhibit CD4+T lymphocyte activation and inflammatory cytokines such as interferon gamma(Interferon-?,IFN-?),interleukin-4(Interleukin-4,IL-4)effect,B7-H3 can occur negatively regulates activation of T cell.Zhang Xiaomin on B7-H3 in atherosclerosis latest preliminary study found that compared with healthy volunteers,patients with carotid atherosclerosis and serum soluble B7-H3(sB7-H3)levels were significantly higher than those in normal,Our previous studies found that patients with acute coronary syndrome serum sB7-H3 and sB7-H4 levels increased with the severity of coronary lesion and its secretion may be an important biological marker of atherosclerosis,its expression level may be for the diagnosis and prognosis of AS has a certain potential value.The previous studies on B7-H3 and B7-H4 are mainly about on tumors,autoimmune diseases and acute and chronic allograft rejection and other diseases,and the relationship between B7-H3,B7-H4 and atherosclerosis research at home and abroad are rare.Objective To investigate the intensive atorvastatin therapy on B7-H3,B7– H4 in Peripheral blood monocytes of patients with unstable angina undergoing percutaneous coronary intervention.Methods The patients with unstable angina were randomized to pretreatment with either an intensive dose(80 mg/day,n = 40)or a conventional dose(20 mg/day,n = 40)of atorvastatin.Two groups of patients were treated with atorvastatin at the dose of 48 h before PCI,Peripheral blood were subsequently obtained prior to PCI,and also 18-24 h after PCI.Peripheral blood serum level of IL-4,IL-10,IFN – gamma and sB7-H3,sB7 – H4 were quantified using enzyme-linked immunosorbent assays,Fluorescence-basedquantitive real-time PCR was used to measure levels of peripheral blood monocytes B7-H3 mRNA and B7 – H4 mRNA.Results(1)before PCI,there is no statistically significant differences between the two groups of patients with serum concentration of IL-4,IL-10,IFN-gamma(P>0.05);after PCI,conventional dose group and intensive dose group serum of IL-4 and IFN-gamma were decreased,and the intensive dose group decreased more significantly,the difference was statistically difference(P<0.05);instead,the level of serum IL-10 were significantly higher,and the intensive dose group were higher than conventional dose group,and the difference was statistically significant(P<0.05);(2)before PCI,no significant difference between the two groups of s B7-H3,sB7-H4 concentration(P>0.05);after PCI,two groups of concentration levels of sB7-H3,sB7-H4 the were increased,the intensive dose group levels of sB7-H3 and sB7-H4 were significantly higher than conventional dose group,the difference was statistically significant(P<0.05);(3)before PCI,the expression level of B7-H3 mRNA and B7-H4 mRNA showed no significant difference(P>0.05).After PCI,the conventional dose group B7-H3 and B7-H4 mRNA expression levels were not significantly changed,there was no statistically significant difference(P>0.05);post-PCI,the expression of B7-H3 mRNA and B7-H4 mRNA was significantly higher,and intensive dose group were significantly higher,the difference was statistically significant(P<0.05);(4)linear correlation analysis: B7-H3 mRNA and IL-10 positive correlation,r=0.629(P<0.05);B7-H3 mRNA was negatively correlated with IL-4 and IFN-gama,(r=-0.342,r=-0.417,P<0.05);B7-H4 mRNA and IL-10 were positively correlated(r=0.599,P<0.05);negative correlations between B7-H4 mRNA and IL-4,IFN-levels(r=-0.391,r=-0.458,P<0.05).Conclusion Intensive dose atorvastatin treatment improve post-PCI immune inflammation in patients with unstable angina,possibly by promoting the expression of B7-H3,B7 – H4 in Peripheral blood monocytes,but this warrants further investigation.