| Objectives: The present study aimed to explore the association of pro-and antiinflammatory adipocytokines,including serum levels of retional-binding protein-4(RBP-4),pentraxin3(PTX-3),galectin-3(GAL-3),plasminogen activator inhibitor-1(PAI-1),adiponectin(ADP),interleukin-37(IL-37)and netrin-1(NTN1),with the development of coronary atherosclerotic disease(CAD)and coronary stenotic severity and to identify the inflammatory biomarkers for the diagnosis and risk assessment of CAD.Methods:A total of 259 inpatients with chest pain who underwent coronary angiography were enrolled in this study and assigned into CAD group(n=180)and Non-CAD group(n=79).The baseline demographic and clinical characteristics were collected by the cardiologists.The severity of coronary atherosclerotic stenosis was quantitated by the Gensini score.The levels of serum RBP-4,PTX-3,PAI-1,NTN1,IL-37,GAL-3 and ADP were evaluated by enzyme-linked immunosorbent assay(ELISA)kits.The correlations of inflammatory cytokines and coronary stenosis with clinical parameters were assessed using Spearman's rank order test.And the receiver operating characteristic(ROC)curves were constructed to set out the areas under the curve(AUC)and diagnostic cutoff values for the diagnosis of CAD.Results:1 Clinical features: compared with the Non-CAD group,the CAD group had more male patients[75.0%(135/180)vs 62.0%(49/79),P<0.05],the prevalence of hypertension(HT),type 2 diabetes mellitus(T2DM),hyperlipidemia and smoking were significantly higher in CAD group than those in Non-CAD group[68.3%(128/180)vs 51.9%(41/79);38.9%(70/180)vs 20.2%(16/79);42.8%(77/180)vs 19.0%(15/79);61.1%(110/180)vs 35.4%(28/79)all P<0.05].2 The levels of inflammatory adipocytokines :2.1 Detection of pro-inflammatory adipocytokines serum levels by ELISA.The serum levels of RBP-4,PTX-3,PAI-1 and GAL-3 were significantly higher than those in Non-CAD group with the results of 5.79(4.49,6.96)pg/mL vs 3.6(2.07,5.25)pg/mL,3.93(3.18,5.27)ng/mL vs 1.56(0.55,2.34)ng/mL,770.89(712.27,851.58)pg/mL vs 709.79(592.0,775.90)pg/mL,3.35(2.10,4.47)ng/mL vs 1.14(0.56,1.99)ng/mL,respectively(all P<0.05).2.2 Detection of anti-inflammatory adipocytokines serum levels by ELISA.The serum levels of NTN1,IL-37 and ADP were significantly lower than those in Non-CAD group,with the results of 50.45(30.83,69.78)pg/mL vs 89.28(60.08,126.26)pg/mL,87.74(72.14,108.28)pg/mL vs 185.38(153.32,218.21)pg/mL and 8.13(6.88,9.21)ng/mL vs 11.24(10.18,12.14)ng/mL,respectively(all P<0.05).3 The levels of serum inflammatory adipocytokines in 1-,2-,3-vessels CAD subgroups.The results of PAI-1 were 711.00(597.41,783.56)pg/mL,740.10(677.13,797.14)pg/mL,760.56(723.80,819.33)pg/mL and 822.18(748.45,929.55)pg/mL in Non-CAD group,1-,2-,3-vessels CAD subgroups,andthe differences were statistically significant(all P<0.05).Meanwhile,in different groups,the concentrations of serum inflammatory adipocytokines were statistically different,which results were 184.58(149.45,217.69)pg/mL,101.68(89.08,124.38)pg/mL,87.00(71.16,100.54)pg/mL,79.10(43.26,92.47)pg/mL(all P<0.05).Additionally,the concentrations of serum inflammatory adipocytokines ADP in Non-CAD group,1-,2-,3-vessels CAD subgroups were significantly different(all P < 0.05).The results were 11.23(10.10,12.12)ng/mL,8.91(7.97,9.68)ng/mL,8.22(6.97,8.77)pg/ mL,7.03(5.50,8.17)ng/mL,respectively.4 The correlation of the serum levels of inflammatory adipocytokines with coronary stenosis and clinical characteristics.4.1 The serum levels of RBP-4,PTX-3,PAI-1 and GAL-3 were significantly positively correlated with the Gensini Score(Rs=0.313,0.278,0.524,0.670)(all P<0.05);while the correlation between the serum levels of IL-37,ADP and Gensini Score was sinificant negative(Rs=-0.650,-0.493)(all P<0.05).4.2 All of the serum levels of RBP-4,PTX-3,PAI-1,GAL-3,NTN1,IL-37 and ADP had significant association with each other(all P<0.05).4.3 The correlations of inflammatory factors with clinical characteristics.4.3.1 The correlation between the serum levels of inflammatory adipocytokines and classical risk factors.The serum levels of GAL-3 and PTX-3 were positively correlated with dyslipidaemia(Rs=0.152,0.152),while the serum levels of NTN1,IL-37 and ADP were negatively correlated with dyslipidaemia(Rs=-0.146,-0.140,-0.218)(all P<0.05).The serum levels of GAL-3,PTX-3 and RBP-4 were positively correlated with HTN(Rs=0.203,0.180,0.122),conversely,the serum levels of IL-37 and ADP were negatively correlated with HTN(Rs=-0.143,-0.142)(all P<0.05).The serum levels of GAL-3,PTX-3 and RBP-4 were positively correlated with T2MD(Rs=0.144,0.142,0.141),inversely,the serum levels of IL-37 and ADP were negatively correlated with T2MD(Rs=-0.186,-0.171)(all P<0.05).In addition,the serum concentrations of GAL-3 and RBP-4 were positively correlated with stroke(Rs=0.156,0.133)(all P<0.05).And the serum levels of PTX-3 were positively correlated(Rs=0.176),while NTN1,IL-37 and ADP negatively correlated(Rs=-0.139,-0.177,-0.139)with smoking(all P<0.05).4.3.2 The correlation between the serum levels of inflammatory adipocytokines and chest pain.The serum levels of PAI-1,GAL-3,PTX-3 and RBP-4 were positively correlated with chest pain(Rs=0.146,0.155,0.380,0.268),the serum levels of NTN1,IL-37,ADP were negatively correlated with chest pain(Rs=-0.216,-0.360,-0.273),the differences were statistically significant(all P<0.05).4.3.3 The correlations of inflammatory factors with clinical characteristics.The serum levels of PAI-1 were associated with aortic valve calcification and BMI(Rs=0.129,0.217),the differences were statistically significant(all P<0.05).The serum levels of NTN1 was negatively correlated with abnormal ventricular wall motion and BMI(Rs=-0.162,-0.201),the differences were statistically significant(all P<0.05).The serum levels of IL-37 was negatively correlated with abnormal ventricular wall motion,total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and Cr(Rs=-0.194,-0.124,-0.126,-0.154),the differences were statistically significant(all P<0.05).The serum levels of GAL-3 was positively correlated with heart rate(HR),systolic blood pressure(SBP),BNP and abnormal ventricular wall motion(Rs=0.126,0.133,0.204,0.226),the differences were statistically significant(all P<0.05).The serum levels of ADP were associated with BNP,LVEDD,LVSDD,EF,abnormal ventricular wall motion,TC,LDL-C,Cr and(Rs=-0.181,-0.129,-0.136,0.175,-0.234,-0.132,-0.162,-0.151),the differences were statistically significant(all P<0.05).The serum levels of PTX3 was positively correlated with BNP,abnormal ventricular wall motion and Cr(Rs=0.193,0.161,0.165),the differences were statistically significant(all P<0.05).The serum levels of RBP-4 were associated with BNP,EF,abnormal ventricular wall motion,triglyceride(TG)and high density lipoprotein cholesterol(HDL-C)(Rs=0.187,-0.154,0.135,0.149,-0.154),the differences were statistically significant(all P<0.05).5 ROC curve analysis showed that the areas under the curve(AUC)of the anti-inflammatory factor,NTN1,IL-37 and ADP,for the diagnosis of CAD was 0.771(95%CI:0.703-0.890),0.908(95%CI:0.703-0.840),0.870(95%CI: 0.820-0.920),and the optimal cut-off value was 71.6pg/ml,140.86 pg/ml,9.8ng/ml,the sensitivities were 70.89%,83.54%,82.28%,and the specificities were 75.88%,90.0%,85.37%,respectively(all P<0.05).ROC curve analysis also demonstrated that the AUC of the pro-inflammatory factor RBP-4,PTX-3,PAI-1,GAL-3 for the diagnosis of CAD was 0.769(95%CI: 0.700-0.837),0.914(95%CI:0.875-0.943),0.699(95%CI: 0.629-0.769),0.853(95%CI:0.803-0.903),the optimal cut-off value were 4.03 pg/ml,2.41 ng/ml,724.5pg/ml,2.41ng/ml,the sensitivities were 91.76%,96.47%,74.57%,68.64%,and the specificities were 61.27%,82.19%,54.44%,86.08%,respectively(all P<0.05).Conclusions:1 The serum levels of inflammatory adipocytokines RBP-4,PTX-3,PAI-1 and GAL-3 were significantly higher,while the levels of NTN1,IL-37 and ADP were significantly lower,in CAD group than those in Non-CAD group.Therefore,these newly found biomarkers may be recommended as diagnositic tools for CAD.2 Gensini Score,as an international indicator of the quantitative assessment of coronary angiographic stenosis was positively related with the serum level of RBP-4,PTX-3,PAI-1 and GAL-3,nevertheless,negatively related with IL-37 and ADP.The above pro-and anti-inflammatory adipocytokines indirectly reflected the severity of coronary artery stenosis and were hopefully used as biological markers to assess the risk of CAD.3 The serum inflammatory adipocytokines,RBP-4,PTX-3,PAI-1, GAL-3,IL-37 and ADP,were significantly correlated with the classic risk factors of CAD,hypertension,dyslipdemia,diabetes mellitus and smoking,which may be used as important biomarkers for the clinical diagnosis and risk assessment of CAD. |
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