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Effect And Mechanism Of Adipokine CTRP3 On Coronary Artery Calcification In Type 2 Diabetes Patients

Posted on:2022-09-17Degree:MasterType:Thesis
Country:ChinaCandidate:X W CuiFull Text:PDF
GTID:2504306554989749Subject:Internal Medicine
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Objective: To investigate the effect of adipokine CTRP3 on coronary artery calcification in patients with type 2 diabetes.To elucidate the mechanism of CTRP3 on osteoblastic differentiation of VSMCs induced by hyperglycemia and hyperlipidemia.The aim is to provide new ideas for the early detection of coronary artery calcification and clinical treatment.Methods:1.Correlation of CTRP3 and coronary artery calcification119 patients with coronary heart disease who were enrolled in the Department of Cardiology,the Second Hospital of Hebei Medical University from January 2019 to January 2021.The patients were distributed into 3groups: no coronary calcification without diabetes group,coronary calcification without diabetes group,coronary calcification combined with diabetes group.General clinical data(age,sex,height,weight,blood pressure,heart rate,and left ventricular ejection fraction)were collected for all subjects.Laboratory examination data [Hb A1 c,FBG,B-type natriuretic peptide(BNP),myocardial enzymes(MYO,CK,CKMB,LDH,HBDH),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),hs-CRP,uric acid] were collected.CTRP3 levels were measured using an enzyme-linked immunosorbent assay(ELISA)on the study subjects.2.The mechanism of CTRP3 inhibiting osteogenic differentiation of VSMCsVSMCs were inoculated on 6-well plates and cultured at 37℃.When cells reached 80% fusion,they were randomly grouped as follows: vehicle group,hyperglycemia and hyperlipidemia(HGHL)group,CTRP3 group,JW74 group,CTRP3+WT-β-catenin group and CTRP3+JW74+WT-β-catenin group.Calcium concentration was quantified in VSMCs using a calcium concentration kit.The expression of osteogenic-related proteins OC,BMP-2and COL-I were detected by Western Blot.The translocation of β-catenin of VSCMs was observed by using laser scanning confocal microscopy(LSCM).3.Statistical analysisStatistical analysis of the data was performed using SPSS 22.0 statistical software.Measures that conformed to a normal distribution were expressed as mean ± standard deviation.T-test was used for comparison between the two groups and one-way ANOVA was used for comparisons between multiple groups.Measures that were skewed were expressed as median ± interquartile range and comparisons between groups were made using the rank-sum test.The effect of different variables on coronary artery calcification was calculated using logistic regression analysis.The area under the ROC curve(AUC)was used as an index of precision to assess the diagnostic performance of the markers.P<0.05 was considered as a statistically significant difference.Results:1.The effect of CTRP3 on coronary artery calcification1.1 One-way ANOVA and chi-square test showed that gender,age,glycated haemoglobin,fasting blood glucose,CKMB,TC,TG,HDL-C,CTRP3 were significantly different among the three groups.CTRP3 concentrations were significantly lower in the coronary calcification combined with diabetes group compared to the coronary calcification without diabetes group and the no coronary calcification without diabetes group.1.2 Logistic regression analysis of the data demonstrated that CTRP3 was a protective factor for coronary artery calcification.The area under the ROC curve for serum CTRP3 levels to determine coronary artery calcification was0.717,with a cut-off value of 36.25ng/m L giving a sensitivity of 54.6% and specificity of 87.0%(95% CI: 0.586-0.826;P=0.002)for predicting coronary calcification.2.Mechanism of inhibiting osteogenic differentiation of VSCMs2.1 HGHL promoted osteogenic differentiation of VSMCs in a time-dependent manner.2.2 HGHL stimulation increased the calcium concentration in VSMCs and promoted the nuclear translocation of β-catenin.2.3 After VSMCs were pretreated with CTRP3,the intracellular calcium concentration was significantly reduced and the expressions of OC,BMP-2and COL-I were inhibited in the VSCMs.2.4 CTRP3 can significantly inhibit the nuclear translocation of β-catenin.Overexpression of β-catenin in cells significantly reduced the inhibitory effect of CTRP3 on osteoblastic differentiation of VSMCs.Conclusions:1.The level of CTRP3 is decreased in patients with coronary artery calcification,and CTRP3 has predictive value in coronary artery calcification.2.CTRP3 inhibits the osteogenic differentiation of VSCMs by inhibiting the nuclear translocation of β-catenin induced by HGHL.
Keywords/Search Tags:Coronary artery, Vascular calcification, CTRP3, Smooth muscle cells, Osteogenic differentiation
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