Plasma S100A12 Research Articles

Studying the association of plasma S100A12 and noninfectious pulmonary complication in infants and young children following cardiopulmonary bypass

Objective To examine the kinetics of plasma S100A12 and soluble receptor for advanced glycation end products (sRAGE) in infants and young children undergoing cardiopulmonary bypass ( CPB),and to investigate whether they could protective the occurrence of noninfectious pulmonary complication (NPC) after cardiac surgery.Methods This was a case-control study.The subjects included all children aged ＜3 years old who underwent cardiac surgery with CPB during the period from June 1st to July 31st 2011.The patient who showed pulmonary inflammation or had abnormal liver or renal function before surgery was excluded.The remain patients were divided into 2 groups according to whether they had developed NPC postoperatively.Twenty patients were grouped into NPC because they developed the complications of pleural effusion,chylothorax,partial lung collapse,pulmonary hypertensive crisis,airway disorders,pneumothorax,pneumomediastinum,or phrenic nerve palsy.Forty patients were categorized into the no-NPC group.Plasma concentrations of S100A12 and sRAGE were measured using ELISA at baseline,before CPB,immediately after CPB,1 h,12 h and 24 h after operation.Differences concentrations between two groups were analyzed with t test.A stepwise logistic regression analysis was used to indentify the independent risk factor for NPC.A P value ＜0.05 was considered statistically significant.Results Plasma levels of S100A12 and sRAGE dramatically increased immediately after CPB ( P ＜ 0.01 ).The levels of sRAGE dropped to lower than baseline level (P ＜0.05),while S100A12 was still at high level 24h after operation (P ＜0.01 ).Levels of S100A12 and sRAGE immediately after CPB in NPC group were significantly higher than the no-NPC group (P ＜ 0.05).Twenty-four hours after operation,levels of S100A12 were still higher in NPC group than no-NPC (P ＜ 0.01 ),while levels of sRAGE were similar in the two groups ( P ＞ 0.05 ).In the stepwise logistic regression analysis,plasma S100A12 level immediately after CPB remained as a independently predictor for postoperative NPC (OR =1.042,95％ CI:1.010 ～ 1.076,P =0.011 ).Levels of S100A12 immediately after CPB were positively associated with mechanical ventilation time ( r =0.47,P ＜ 0.01 ),duration of surgical Intensive Care Unit ( r =0.407,P =0.002) and hospital stay ( r =0.421,P =0.01 ).Conclusions Plasma levels of S100A12 and sRAGE were significantly increased immediately after CPB and the elevated plasma S100A12 immediately after CPB served as an early reliable biomarker of the occurrence and the prognosis of NPC after CPB in infants and young children. Key words: S100A12; Soluble advanced glycation end products (sRAGE); Noninfectious pulmonary complication (NPC) ; Cardiopulmonary bypass; cardiac surgery; Congenital heart disease; Infant and young children ; Case-control; Correlation.

Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children

IntroductionAcute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).MethodsConsecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation.ResultsFifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001).ConclusionsElevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.

S100A12 as a Marker to Predict Cardiovascular Events in Patients With Chronic Coronary Artery Disease

S100A12, a calgranulin family protein released from white blood cells, is involved in inflammatory cardiovascular disease. It was hypothesized that the plasma level of S100A12 can be used to predict outcome in patients with chronic coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of S100A12 in patients with stable CAD. A total of 652 patients with stable CAD were studied. All patients underwent percutaneous coronary intervention and successful revascularization. Major adverse cardiovascular events (MACE) were defined as a composite of events of CHF, recurrence of angina pectoris, acute myocardial infarction, stroke, critical arrhythmia, intervention to peripheral arteries and cardiac death. The mean follow-up period was 973±639 days. MACE occurred in 108 patients (16.6%). Plasma S100A12 level had a significant positive correlation with high-sensitivity C-reactive protein (hs-CRP) level. On Kaplan-Meier curve analysis the incidence of MACE was significantly different among S100A12 quartiles (P=0.026). The highest S100A12 quartile (Q4) had a significantly higher MACE rate than the lowest quartile (Q1) (P=0.002). In contrast, hs-CRP was not significant for predicting MACE in the present subjects (P=0.074). A Cox proportional hazard model showed that S100A12 was an independent factor for predicting MACE in multivariate models. S100A12 could be a novel biomarker for predicting cardiovascular events for predicting MACE in patients with stable CAD.

Plasma S100A12 Levels and Peripheral Arterial Disease in End-Stage Renal Disease

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p < 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR] 5.71; 95% confidence interval [CI] 1.29–25.3; p = 0.022) was identified as an independent factor associated with PAD prevalence. Another factor associated with PAD prevalence was the ankle-brachial index (OR 0.54; 95% CI 0.40–0.74; p < 0.001). Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD.

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

Increased Plasma S100A12 (EN-RAGE) Levels in Hemodialysis Patients with Atherosclerosis

Background: S100A12, also known as EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) is a ligand for RAGE, and has been proposed to contribute to the development of atherosclerosis. In this study, we examined the plasma S100A12 concentration in patients with ESRD and undergoing hemodialysis (HD) and evaluated the relation between S100A12 level and carotid intimal media thickness (IMT) by ultrasound. Methods: We measured plasma S100A12 concentration in 72 HD patients and 42 control subjects. IMT of the carotid artery was measured by high-resolution B-mode ultrasonography in 46 HD patients. Results: The mean plasma S100A12 level was 2.3-fold higher in HD patients than in control subjects (25.0 ± 2.32 vs. 10.7 ± 0.97 ng/ml, p < 0.001). Stepwise multiple regression analysis identified circulating white blood cell count as a positive independent determinant and total cholesterol and serum albumin levels as negative independent determinants of plasma S100A12 concentration. The maximum IMT was positively correlated with plasma S100A12 level. Stepwise multiple regression analysis also identified plasma S100A12 as a significant independent determinant of the maximum IMT. Conclusion: These findings suggest that S100A12 protein is involved in the acceleration of atherosclerosis in HD patients.

Plasma S100A12 Concentrations in Peritoneal Dialysis Patients and Subclinical Chronic Inflammatory Disease

S100A12 is a ligand for the receptor for advanced glycation end products. It has been shown that S100A12 induces expression of adhesion molecules, and mediates activation and migration of monocytes/macrophages. Circulating S100A12 may be involved in chronic inflammation. We previously reported increased S100A12 levels in patients with non-insulin-dependent diabetes mellitus and hemodialysis. A high peritoneal solute transport rate may be associated with encapsulating peritoneal sclerosis and mortality. We measured plasma S100A12 levels in peritoneal dialysis patients and evaluated a possible relation between the increased plasma S100A12 levels in peritoneal dialysis patients and the high peritoneal solute transport rate. Subjects included 36 patients (mean age +/- SE, 46.0 +/- 12.0 years) with no apparent infection and no malignancy who had been undergoing peritoneal dialysis for 36.5 +/- 3.9 months. We developed an enzyme-linked immunosorbent assay system to measure plasma S100A12 levels. A peritoneal equilibrium test was performed and subjects were categorized as high and high-average (H) (n = 14) or low and low-average (L) (n = 22) transporters. Plasma S100A12 concentrations were significantly higher in peritoneal dialysis patients (21.6 +/- 3.0 ng/mL) than in control subjects (n = 42; 10.8 +/- 1.0 ng/mL). Plasma S100A12 concentrations were also higher in the H group (28.2 +/- 6.1 ng/mL) than in the L group (14.2 +/- 2.0 ng/mL). These results suggest that S100A12 may be a sensitive marker of subclinical inflammation and that an increased S100A12 level may be related to the high peritoneal solute transport rate.

Circulating Soluble Receptor for Advanced Glycation End Products Is Inversely Associated with Glycemic Control and S100A12 Protein

The interaction of advanced glycation end products, including Nepsilon-(carboxymethyl)lysine-protein adducts (CML) and S100A12 protein, with their cellular receptor (RAGE) is implicated in the pathogenesis of diabetic vascular complications. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which, by neutralizing the action of advanced glycation end products, might exert a protective role against the development of cardiovascular disease. The objective of the study was to investigate whether plasma sRAGE levels are associated with glycemic control, proinflammatory factors, or circulating ligands of RAGE such as plasma CML and S100A12 protein. We studied 160 subjects, 84 subjects with type 2 diabetes (aged 60 +/- 7 yr) and 76 nondiabetic controls (aged 45 +/- 10 yr). Plasma sRAGE was lower in diabetic patients than controls [141 (53-345) vs. 735 (519-1001) pg/ml, median (interquartile range), P < 0.0001], whereas CML levels were higher in diabetic patients than controls [67.9 (46.0-84.7) vs. 43.4 (28.0-65.0) microg/ml, P < 0.0001]. In stepwise regression analysis of the whole data set, hemoglobin A1c, insulin resistance (as homeostasis model assessment), and C-reactive protein were independently associated with plasma sRAGE, whereas age was not. In a subgroup of 26 diabetic and 24 nondiabetic subjects of similar age (54 +/- 3 yr), plasma S100A12 levels were higher in diabetic subjects [49 (39-126) vs. 28 (21-39) ng/ml]. Moreover, low sRAGE and high S100A12 were strongly associated with increased risk for cardiovascular disease (Framingham score). In this subgroup, the plasma S100A12 level was the only determinant of plasma sRAGE concentration. Plasma level of sRAGE is down-regulated in chronic hyperglycemia; among its ligands, S100A12 protein, but not CML, appears to be associated with this effect.

Increased Plasma S100A12 (EN-RAGE) Levels in Patients with Type 2 Diabetes

S100A12, also called EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) or calcium-binding protein in amniotic fluid-1, is a ligand for RAGE. It has been shown that S100A12 induces adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in the vascular endothelial cell and mediates migration and activation of monocytes/macrophages through RAGE binding and that infusion of lipopolysaccharide into mice causes time-dependent increase of S100A12 in the plasma. Therefore, circulating S100A12 protein may be involved in chronic inflammation in the atherosclerotic lesion. In this study, we developed an ELISA system that uses specific monoclonal antibodies against recombinant human S100A12 to measure plasma S100A12 levels in patients with diabetes. On using our S100A12 ELISA system, the coefficients of variation of intra- and interassay were less than 4 and 9%, respectively. The analytical lower detection limit was 0.2 ng/ml. When plasma S100A12 levels were measured by this system, the concentrations were more than twice as high in the patients with diabetes, compared with those without. Using univariate analysis in all subjects, plasma S100A12 concentrations correlated with hemoglobin A1c, fasting glucose, high-sensitivity C-reactive protein and white blood cell count. Stepwise multiple regression analyses, however, revealed that only white blood cell count and hemoglobin A1c remained significant independent determinants of plasma S100A12 concentration. These results suggest that plasma S100A12 protein levels are regulated by factors related to subclinical inflammation and glucose control in patients with type 2 diabetes.