Ses and plays a distinct role in inflammation and immunity [17]. The

Ses and plays a distinct role in inflammation and immunity [17]. The Wnt pathways are regulated by multiple families of secreted antagonists, including soluble frizzled-related receptors and DKKs, the best-studied being DKK-1. DKK-1 has been implicated in cancer, brain ischemia, and bone disease [6,7,8,18]; previous studies haveFigure 3. Association of tertiles of DKK-1 level and major adverse coronary 50-14-6 web Events (MACE) (P,0.001). doi:10.1371/journal.pone.0054731.gDickkopf-1 Is Associated with ACS PatientsTable 2. Baseline Characteristics of Patients With and Without Major Adverse Coronary Events.Variables Age (yr) Male, no. ( ) Body mass index (kg/m2) Hypertension, no. ( ) SBP (mmHg) DBP (mmHg) Diabetes, no. ( ) Smoker, no. ( ) Total cholesterol level (mmol/L) Triglycerides level (mmol/L) HDL-cholesterol level (mmol/L) LDL-cholesterol level (mmol/L) Blood glucose (mmol/L) Cr (mmol/L) CK activity (mmol/L) cTnI level (ng/ml) Uric acid level (mmol/L) Hs-CRP level (pg/ml) DKK-1 level (pg/ml) Cardiovascular disease, no. vessels involved, no. ( ) 1 vessel 2 vessels 3 vessels Stenosis degree, no. ( ) 50?5 75 doi:10.1371/journal.pone.0054731.tWith MACE (n = 44) 60610 30 (68.2) 26.063.1 37 (84.1) 131612 75610 23 (52.3) 27 (61.4) 5.0960.67 1.9260.47 1.0760.16 2.8760.57 6.7661.00 87.768.86 121.36186 0.6862.1 317640 3.4461.38Without MACE (n = 247) 56610 163 (66.0) 26.564.9 145 (58.7) 131615 77611 54 (21.9) 114 (46.2) 4.5960.85 1.6960.58 1.2160.27 2.6460.64 6.2660.88 87.169.00 95.36118 1.2666.0 314646 1.7661.62P value0.039 0.777 0.569 0.001 0.865 0.327 0.001 0.063 ,0.001 0.014 ,0.001 0.028 0.001 0.694 0.258 0.580 0.690 ,0.001 ,0.001 0.10 (22.7) 19 (43.2) 15 (34.1)95 (38.5) 82 (33.2) 70 (28.3) 0.16 (36.4) 28 (63.6)109 (44.1) 138 (55.9)Table 3. Binary Logistic Regression Analysis of Cardiovascular Risk Predictors for Patients with ACS.Variables Age Sex Body mass index Hypertension Diabetes Smoker Hypercholesterolemia Triglyceride level LDL-C level HDL-C level Hs-CRP levelOR 1.047 0.487 0.872 0.167 0.370 0.514 2.971 0.805 1.411 0.093 1.395 8.95 CI 0.993?.103 0.135?.760 0.745?.021 0.048?.577 0.137?.003 0.155?.698 1.383?.385 0.339?.912 0.565?.522 0.009?.977 1.072?.815 3.176?2.P value0.090 0.272 0.089 0.005 0.051 0.275 0.005 0.623 0.461 0.048 0.013 ,0.Figure 4. Log DKK-1 in patients with ACS in 3 subgroups by GRACE score. Data are median (range). doi:10.1371/journal.pone.0054731.gDKK-1 levelOR, odds ratio; 95 CI, 95 confidence interval. doi:10.1371/journal.pone.0054731.tDickkopf-1 Is Associated with ACS PatientsFigure 5. Receiver operating characteristic curve analysis of predictive models for ACS patients. The sensitivity and specificity for each model was 56.8 and 51.4 ; 84.1 and 64.4 ; 75.0 and 63.2 ; 81.8 23977191 and 71.7 . doi:10.1371/journal.pone.0054731.gshown a close association of serum levels of DKK-1 and atherosclerotic diseases such as premature myocardial infarction [19] or ischemic cerebrovascular disease [20]. The increased expression of DKK-1 in advanced carotid plaques enhancing the inflammatory interaction between platelets and JI 101 site endothelial cells might drive the inflammatory loop [5], Overexpression of DKK-1 was found in macrophages and endothelial cells, and immunostaining of thrombus material from the site of plaque rupture showed strong immunoreactivity in platelet aggregates. As with previous findings [5,19] we found plasma levels of DKK-1 greater in patients with STEMI than NSTE-ACS, and plasma levels of DKK-1 positively correlated wi.Ses and plays a distinct role in inflammation and immunity [17]. The Wnt pathways are regulated by multiple families of secreted antagonists, including soluble frizzled-related receptors and DKKs, the best-studied being DKK-1. DKK-1 has been implicated in cancer, brain ischemia, and bone disease [6,7,8,18]; previous studies haveFigure 3. Association of tertiles of DKK-1 level and major adverse coronary events (MACE) (P,0.001). doi:10.1371/journal.pone.0054731.gDickkopf-1 Is Associated with ACS PatientsTable 2. Baseline Characteristics of Patients With and Without Major Adverse Coronary Events.Variables Age (yr) Male, no. ( ) Body mass index (kg/m2) Hypertension, no. ( ) SBP (mmHg) DBP (mmHg) Diabetes, no. ( ) Smoker, no. ( ) Total cholesterol level (mmol/L) Triglycerides level (mmol/L) HDL-cholesterol level (mmol/L) LDL-cholesterol level (mmol/L) Blood glucose (mmol/L) Cr (mmol/L) CK activity (mmol/L) cTnI level (ng/ml) Uric acid level (mmol/L) Hs-CRP level (pg/ml) DKK-1 level (pg/ml) Cardiovascular disease, no. vessels involved, no. ( ) 1 vessel 2 vessels 3 vessels Stenosis degree, no. ( ) 50?5 75 doi:10.1371/journal.pone.0054731.tWith MACE (n = 44) 60610 30 (68.2) 26.063.1 37 (84.1) 131612 75610 23 (52.3) 27 (61.4) 5.0960.67 1.9260.47 1.0760.16 2.8760.57 6.7661.00 87.768.86 121.36186 0.6862.1 317640 3.4461.38Without MACE (n = 247) 56610 163 (66.0) 26.564.9 145 (58.7) 131615 77611 54 (21.9) 114 (46.2) 4.5960.85 1.6960.58 1.2160.27 2.6460.64 6.2660.88 87.169.00 95.36118 1.2666.0 314646 1.7661.62P value0.039 0.777 0.569 0.001 0.865 0.327 0.001 0.063 ,0.001 0.014 ,0.001 0.028 0.001 0.694 0.258 0.580 0.690 ,0.001 ,0.001 0.10 (22.7) 19 (43.2) 15 (34.1)95 (38.5) 82 (33.2) 70 (28.3) 0.16 (36.4) 28 (63.6)109 (44.1) 138 (55.9)Table 3. Binary Logistic Regression Analysis of Cardiovascular Risk Predictors for Patients with ACS.Variables Age Sex Body mass index Hypertension Diabetes Smoker Hypercholesterolemia Triglyceride level LDL-C level HDL-C level Hs-CRP levelOR 1.047 0.487 0.872 0.167 0.370 0.514 2.971 0.805 1.411 0.093 1.395 8.95 CI 0.993?.103 0.135?.760 0.745?.021 0.048?.577 0.137?.003 0.155?.698 1.383?.385 0.339?.912 0.565?.522 0.009?.977 1.072?.815 3.176?2.P value0.090 0.272 0.089 0.005 0.051 0.275 0.005 0.623 0.461 0.048 0.013 ,0.Figure 4. Log DKK-1 in patients with ACS in 3 subgroups by GRACE score. Data are median (range). doi:10.1371/journal.pone.0054731.gDKK-1 levelOR, odds ratio; 95 CI, 95 confidence interval. doi:10.1371/journal.pone.0054731.tDickkopf-1 Is Associated with ACS PatientsFigure 5. Receiver operating characteristic curve analysis of predictive models for ACS patients. The sensitivity and specificity for each model was 56.8 and 51.4 ; 84.1 and 64.4 ; 75.0 and 63.2 ; 81.8 23977191 and 71.7 . doi:10.1371/journal.pone.0054731.gshown a close association of serum levels of DKK-1 and atherosclerotic diseases such as premature myocardial infarction [19] or ischemic cerebrovascular disease [20]. The increased expression of DKK-1 in advanced carotid plaques enhancing the inflammatory interaction between platelets and endothelial cells might drive the inflammatory loop [5], Overexpression of DKK-1 was found in macrophages and endothelial cells, and immunostaining of thrombus material from the site of plaque rupture showed strong immunoreactivity in platelet aggregates. As with previous findings [5,19] we found plasma levels of DKK-1 greater in patients with STEMI than NSTE-ACS, and plasma levels of DKK-1 positively correlated wi.