Implication Of Adropin In Insulin Resistance And Pathogenesis Of Coronary Atherosclerotic Heart Disease

PartI Implication of adropin in coronary atherosclerotic heartdisease and in stent restenosisObjective: To explore the role of adropin in coronary atherosclerotic heart disease(CAD) and in stent restenosis (ISR), and to evaluate the relationship of adropin and insulinresistance (IR).Materials and methods: A totle of338consecutive patients with chest pain weredivided into CAD group (stenosis≥50%)(n=258) and control group (stenosis <50%)(n=80) by coronary angiography. The CAD group were furher divided into single-vesseldisease (n=84) group and multi-vessel disease group (n=174).176cases received coronarystent implantation1year ago were divided into ISR group (n=18) and non-ISR group(n=158) by review of coronary angiography. Adropin, fasting plasma glucose, insulin,hsCRP, homocysteine levels and lipid profiles were measured, insulin resistance index (IRI)was calculated. Multivariate analysis was performed to assess risk factors for CAD,muti-vessel disease, and ISR.Results:⑴Fasting plasma glucose, insulin, IRI, hypersensitive C reactive protein(hsCRP), homocysteine levels in CAD group were significantly higher, adropin wassignificantly lower than those in control group (P<0.05～0.01). Male, smoking, IRI≥2.69were more common in CAD group. Fasting plasma glucose, hsCRP, IRI were significantlyhigher in multi-vessel disease group than those in single-vessel diseasegroup(P<0.05).Although adropin had no significant difference between multivessel diseasegroup and single-vessel disease group, adropin still had some predictive value inmultivessel disease. Fasting plasma insulin, hsCRP, IRI, number of stent, percentage ofdiabetes and bare metal stent proportion were significantly higher in ISR group than thosein non-ISR group. But the adropin concentration was significantly lower than that in non-ISR group (P<0.05).⑵Multivariate logistic regression analysis revealed that male, old age, hypertension,IRI≥2.69, hsCRP≥10mg/L, adropin≤53.74pg/ml were independent risk factors for CAD(P<0.05～0.01). hsCRP≥10mg/L was independent risk factor for coronary multi-vesseldisease (P<0.01);The application of bare-metal stent was independent risk factor for theISR (P <0.05).⑶ROC curve analysis results suggest that: hsCRP and adropin could predicted CADsignificantly, and the areas under ROC curve were0.724and0.641(P<0.01). hsCRP couldpredicted multi-vessel disease, and the area under ROC curve were0.622(P<0.05)..⑷Correlation analysis showed that adropin was negatively associated with IRI (γ=-0.302, P=0.001), hsCRP (γ=-0.206, P=0.024) and homocysteine (γ=-0.274, P=0.008).Conclution: The lower adropin level is a risk factor for CAD and ISR. Adropin wasnegatively correlated with IRI, hsCRP and homocysteine.PartⅡ Implication of adropin in insulin resistanceObjective: To explore the dynamic change of plasma adropin concentration with IRprocess, and to find out the function of adropin in AS.Methods: Four weeks old SD rats were divided into high-fat diet group (n=40) andcontrol group (n=20). Blood samples were collected by cutting tail at1st,3rd,5th,8th,12th,16th,20th,24th week. Adropin, fasting plasma glucose, insulin, totle cholesterol,triglycerides were measured. The Euglycemic hyperinsulinemic clamp technique GIR andHOMA-IR were used to identify rat insulin resistance model. Taking the rat’s aorta andstained endoscopic to detect pathological changes. Analyzing the relationgship betweenadropin and aortic intimal hyperplasia and vascular smooth muscle cells (VSMC)proliferation and internal migration.Results:⑴Euglycemic hyperinsulinemic clamp technique and the HOMA–IR model showthat most of the rats were able to become IR model after16weeks of high sugar high fatfeeding. The2assessment methods for IR has a good correlation.⑵After16weeks by high sugar high fat feeding, the body weight,fasting plasmaglucose, insulin, IRI, total cholesterol, triglycerides, glucose infusion rate (GIR60-120) of rats increased significantly compared with the control group (P<0.05~0.01), and theadropin concentration was significantly lower in high sugar high fat group than that innormal control group (P <0.01).⑶With the establishment of rat IR model, the plasma adropin concentrationincreased first and then decreased, and reached the peak at about12weeks, the adropinconcentration negatively correlated with hyperinsulinemia and insulin resistance.⑷Rat aortic pathology detection showed intima proliferate obviously with themigration and disorder of smooth muscle cell in high sugar high fat group.⑸Organization PCR analysis showed that adropin expressed in rat livers, brain,aortic intima, aortic medial smooth muscle (VSMC)(202bp). It was the first time to findadropin expressing in aortic intima and VSMC.Conclution: With the establishment of rat IR model, the the plasma adropinconcentration elevated first and then decreased, and had a negative correlation with the IRI.The low adropin level may be related to vascular intima hyperplasia and VSMCproliferation and migration.