Relationship Between Plasma Jagged1 Protein And Coronary Collateral Circulation In Patients With Severe Coronary Artery Stenosis

Background and ObjectiveCoronary heart disease is a series of clinical symptoms of chest pain,and chest tightness due to coronary artery stenosis,spasm or obstruction that cause myocardial ischemia,hypoxia,necrosis,which is currently one of the major diseases that endanger humans.With the deep research on coronary heart disease,percutaneous coronary intervention has become the main treatment,and the amount of coronary artery bypass grafting and percutaneous transluminal coronary angioplasty has gradually decreased.However,for patients with multi-vessel disease,interventional treatment is more complex and more risky,and sometimes the efficacy is not significant.The establishment of arterial collateral circulation(CCC)is particularly important for patients with chronic severe coronary stenosis.Under long-term repeated myocardial ischemia and hypoxia,collateral circulation can relieve myocardial ischemia,reduce myocardial infarct size,inhibit myocardial remodeling,improve cardiac function,and reduce mortality.The establishment of CCC is affected by many factors,and the specific molecular mechanism is still unclear.Studies have found that Notch signaling pathway plays a variety biological roles in the development of the disease.Jagged1 is the first confirmed ligand in Notch receptors on mammalian's cell membrane and plays an important role in muscle formation,angiogenesis and neurodevelopment.Especially in the formation of blood vessels,Jaggedl is widely expressed in endothelial cells.When hypoxia,inflammatory factors,tumor necrosis factor-?and other factors cause damage to endothelial cells,Jagged1 levels increase,participate in repair of endothelial cell damage,and promote angiogenesis.However,whether Jagged1 participates in CCC formation in patients with CHD has not been reported so far.Therefore,by observing the changes of plasma Jagged1 protein level in patients with good CCC and poor CCC,this study explores the relationship between Jagged1 and CCC formation and provides a new research direction for exploring the formation of coronary collateral circulation.MethodsAccording to the results of coronary angiography,we selected 112 patients with coronary heart disease(CHD)and at least one vessel with coronary artery stenosis?95%in Department Elderly of First Affiliated Hospital of Zhengzhou University from June1,2016 to August 25,2017.And 45 cases of normal control group.According to the Rentrop classification,CHD group were further divided into two groups:the collateral circulation well group(Rentrop grading?2)(n=60)and the collateral circulation poor group(Rentrop grading?1)(n=52).The concentrations of Jagged1 protein and vascular endothelial growth factor(VEGF)in plasma of all selected patients were determined by enzyme-linked immunosorbent assay.Gensini scores in CHD group were calculated based on coronary angiography results and Gensini grading,and correlation analysis was performed.SPSS 17.0 was used to analyze the relationship between plasma Jagged1 protein level and VEGF and Gensini scores by t test,ANOVA,?~2 test,Pearson test and multivariate regression analysis.Results:1.The plasma levels of Jagged1 protein[(37.48±9.18)ng/L vs(23.86±9.33)ng/L]and VEGF[(109.30±24.44)pg/L vs 13.13)pg/L]significantly increased,the difference was statistically significant(P<0.01).2.The levels of plasma Jagged1 protein[(31.81±6.35)ng/L vs(42.39±8.40)ng/L]and VEGF levels in CCC-poor group[(94.03±17.96)pg/L vs 122.53±21.48)pg/L were significantly lower than those in CCC good group,the difference was statistically significant(P<0.01).3.The level of HbA1c in patients with poor CCC was significantly higher than that in patients with good CCC[(6.06±0.81)mmol/L vs(5.67±1.05)mmol/L,P=0.028],the difference was statistically significant(P<0.01).4.Pearson correlation analysis show that there was a positive correlation between plasma Jagged1 and Gensini scores(r=0.0403,P=0.001)in CCC good group;VEGF level was positively correlated with Gensini score(r=0.560,P=0.000).Gensini score was positively correlated(r=0.293,P=0.035)in collateral circulation poor group;VEGF level was positively correlated with Gensini score(r=0.296,P=0.033);there was a positive correlation between plasma Jagged1 protein and VEGF in patients with coronary heart disease(r=0.616,P<0.01).5.Multivariate regression analysis show that Jagged1 protein and Gensini score with CCC highly correlated,but its relationship with glucose,HbA1C,etc.needs further study.VEGF(OR=0.974,P=0.074)P>.05,suggesting that the sample size is less relevant.CONCLUSION:1.Jagged1 may participate in the formation of coronary collateral circulation by regulating the secretion of VEGF.2.Jagged1 is an independent predictor of collateral circulation formation,and may become a new direction for the research of coronary heart disease.3.A positive correlation between Jagged1 and Gensini scores,Jagged1 may be a predictor of coronary artery stenosis.