Plasma pentraxin3 and arterial stiffness in men with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) induces inflammation and vascular damage that might contribute to an increased risk of cardiovascular disease (CVD). However, the mechanisms linking OSA and CVD are not fully understood. Pentraxin3 may play a significant role in vascular inflammation and damage. Currently, there is lack of data on pentraxin3 and its role in vascular damage associated with OSA. METHODS: We enrolled 50 males with OSA and 25 controls matched for age and body mass index (BMI). Patients with OSA were further divided into mild and moderate to severe groups. We measured plasma pentraxin3 and evaluated vascular damage using an arterial stiffness parameter--the cardio-ankle vascular index (CAVI)--in all subjects. In the moderate to severe OSA group, pentraxin3 and CAVI were repeatedly measured following continuous positive airway pressure (CPAP) therapy for 1 month. RESULTS: Pentraxin3 levels in the moderate-to-severe OSA group were significantly higher than those in the mild OSA and control groups, with median levels (25th-75th percentile) of 2.36 (1.79-2.78), 1.63 (1.15-2.05), and 1.53 (1.14-2.04) ng/ml, respectively (P < 0.01). Pentraxin3 level was independently correlated with CAVI (coefficient, 0.34 P < 0.01). In the moderate-to-severe OSA group, pentraxin3 and CAVI levels were significantly reduced (P < 0.01 and P = 0.04, respectively) after 1 month of CPAP therapy. CONCLUSIONS: Plasma pentraxin3 and arterial stiffness levels in the moderate-to-severe OSA group were greater than the corresponding levels in patients without OSA. However, pentraxin3 level can be managed by CPAP therapy for OSA.

Pentraxin3 and high-sensitive C-reactive protein are independent inflammatory markers released during high-intensity exercise.

High-intensity exercise shares similarities with acute phase responses of inflammatory diseases. We investigated the influences of acute exercise on inflammatory markers, plasma pentraxin3 (PTX3) and serum high-sensitive C-reactive protein (CRP) (hsCRP). Nine healthy male subjects (41 ± 3 years old) participated. Each subject performed three types of exercise; ergometer exercise at 70% workload of anaerobic threshold (AT) for 30 min (70% AT exercise), peak ergometer exercise (peak EX, 20 watt increase/min until fatigue) and resistance exercises of 70% 1 RM (70% RE) until exhaustion. We measured plasma PTX3, serum hsCRP, lactate, noradrenaline (NOR), white blood cells (WBC), interleukin-6 (IL-6) and myeloperoxidase (MPO), a marker of neutrophil degranulation. The effects of exercise on intracellular PTX3 and MPO in neutrophils were also investigated, by using flow cytometry analysis. Circulating PTX3 and hsCRP significantly increased immediately after 70% RE and peak EX, while they did not increase after 70% AT exercise. The exercise-induced fold increase in PTX3 and hsCRP relative to the resting level was positively correlated with the changes in WBC, NOR, lactate and MPO. The exercise-induced fold increase in IL-6 was positively correlated with that in NOR, but not with that in PTX3 and hsCRP. Neutrophils isolated immediately after 70% RE, but not 70% AT exercise, exhibited lower mean fluorescence for PTX3 and MPO than those from pre-exercise blood. These results provide the evidence that high-intensity exercises significantly increase circulatory PTX3 as well as hsCRP. The release from peripheral neutrophils is suggested to be involved in the exercise-induced plasma PTX3 increase.

Reciprocal contribution of pentraxin 3 and C-reactive protein to obesity and metabolic syndrome.

Pentraxin 3 (PTX3) is an acute-phase protein that shares structural homology with C-reactive protein (CRP). PTX3 is produced in macrophages, endothelial cells, and adipocytes in response to inflammatory stimuli, whereas hepatocytes are the main source of CRP. Because obesity and metabolic syndrome (MetS) are considered chronic inflammatory states, PTX3 might be involved in the pathogenesis of obesity and MetS as well as CRP. Levels of CRP correlated positively with body weight, BMI, waist circumference (WC), fasting plasma glucose and interleukin (IL)-6, and negatively with high-density lipoprotein cholesterol and adiponectin in healthy males. In contrast, PTX3 correlated positively with adiponectin, and negatively with body weight, BMI, WC, and triglyceride. Plasma CRP significantly increased, whereas plasma PTX3 significantly decreased with increasing BMI. Plasma CRP and PTX3 levels were significantly higher and lower, respectively, in individuals who had more than one MetS component compared with those who had none. In conclusion, PTX3 and CRP antagonistically participate in the development of obesity or MetS.

The long pentraxin 3 (PTX3): a novel prognostic inflammatory marker for mortality in acute chest pain.

The long pentraxin 3 (PTX3) is a recently identified member of the pentraxin protein family that includes C-reactive protein. PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli, and elevated plasma levels are found in several conditions including acute coronary syndromes (ACS). The aim of this study was to assess the value of PTX3 as a prognostic marker of mortality and recurrent ischaemic events in a consecutive series of patients admitted with acute chest pain and potential ACS. The patients received follow-up for 24 months. Blood samples were taken on admission for measurement of PTX3, high sensitive C-reactive protein (hsCRP), B-type natriuretic peptide (BNP), and troponin T. All-cause mortality at 24 months in the study cohort was 15.2%. Patients in the upper PTX3 quartiles had a significantly higher death risk than those in the lowest quartile (Q3: hazard ratio [HR] 2.36; 95% CI 1.12-4.99; p = 0.024, and Q4: HR 3.60; 95% CI 1.68-7.72; p = 0.001). Elevated BNP levels were also significantly associated with a fatal outcome (Q3: HR 3.05; 95% CI 1.16-7.99; p = 0.024; and Q4: HR 3.90; 95% CI 1.48-10.26; p = 0.006). Elevation in hsCRP was not associated with increased death risk. As PTX3 predicted mortality independently of BNP, the combination of these two biomarkers showed an incremental prognostic value. PTX3 is a new biomarker related to inflammation that, independently of BNP, strongly predicts long-term all-cause mortality in patients with acute chest pain. The combination of these two biomarkers enhances the prognostic value over either marker alone.

Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia.

OBJECTIVE: To investigate the effect of pitavastatin on asymptomatic atherosclerosis in patients with hypercholesterolemia. METHODS: Thirty-five outpatients with hypercholesterolemia (61.5+/-12.8 yr) were administered 2 mg oral pitavastatin daily for 6 months. Plasma pentraxin 3 (PTX3), a novel inflammatory marker of atherosclerosis, was measured together with the serum hsCRP and carotid-artery intima-media thickness (IMT). RESULTS: Significant improvement of the LDL-C/HDL-C and log (TG/HDL-C) ratios began to be observed from 1 month after using pitavastatin. Significant correlation of the initial PTX3 value was observed with the initial plaque score (PS) (p=0.038, r=0.246), but not between the hsCRP and plasma PTX3 or PS. When patients were divided into 3 groups based on the initial PTX3 values, a significant decrease of the plasma PTX3 was obtained in the highest PTX3 group alone (p=0.034). The change in the plasma PTX3 value (DeltaPTX3) was significantly correlated with the Delta mean IMT during the study period (p=0.008, r=0.456). CONCLUSION: Pitavastatin significantly reduced the elevated plasma levels of PTX3 in patients with hypercholesterolemia by its pleiotropic effect against atherosclerotic inflammation. This study showed for the first time that the plasma PTX3 might be a useful blood parameter for direct detection of active atherosclerotic change.

Identification of Cystatin SN as a novel tumor marker for colorectal cancer.

The goal of this study was to investigate Cystatin SN, a cysteine protease inhibitor, as a novel tumor marker for colorectal cancer (CRC). Gene expression profiles of mRNA from normal tissues and cancer cell lines were performed. Twenty-eight monoclonal antibodies for Cystatin SN were generated and serum Cystatin SN was quantified using ELISA in sera from 159 patients with CRC and 40 healthy controls. Cystatin SN was highly expressed in colon cancer cells. Employing a receiver-operating characteristic curve, we obtained an area under the curve of 0.708 for Cystatin SN, 0.819 for carcinoembryonic antigen (CEA) and 0.703 for carbohydrate antigen 19-9 (CA19-9). The combination assay of Cystatin SN, CEA and CA19-9 showed 62.9% sensitivity and 90.0% specificity. Especially, the sensitivity of the combination assay in stages I and II detection, in which stages curative operation would be possible, was improved over that of the assay testing only for CEA and CA19-9 (from 37.5 to 42.5% in stage I, from 49.0 to 60.8% in stage II). Furthermore, Western blot analysis revealed that Cystatin SN was increased in the urine from patients with CRC. Our results suggest the possibility of utilizing this novel tumor marker that can be tested in urine samples. These observations suggest that Cystatin SN in combination with CEA and CA19-9 is a useful tumor marker for detecting early stage CRC and that it is a unique urinary excretory protein, suggesting that Cystatin SN might be a novel candidate for use in mass screening for CRC.

Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations.

BACKGROUND: The aim of this study was to evaluate the distribution of pentraxin 3 (PTX3) values in healthy subjects and to characterize its relationship with gender, age, body mass index (BMI), lipid profile, and blood sugar levels. METHODS: A Japanese population of 1749 healthy subjects (818 men and 931 women) with a mean (SD) age of 59.6 (11.4) years (range 37-87 years) were examined. RESULTS: Plasma PTX3 levels (PTX3 data are expressed as the geometric mean and confidence intervals) were i) significantly lower in men than in women (1.87 [1.81, 1.94] ng/mL vs. 2.12 [2.05, 2.19] ng/mL, p<0.0001), ii) significantly higher in the high age group (men, lowest quartile 1.62 [1.50, 1.74] ng/mL vs. highest quartile 2.14 [2.02, 2.27] ng/mL, p<0.001; women, lowest quartile 2.05 [1.92, 2.18] ng/mL vs. highest quartile 2.23 [2.02, 2.46] ng/mL, p<0.05), iii) inversely correlated with triglycerides (r=-0.19 in men and r=-0.18 in women, p<0.00001), and BMI (r=-0.16 in men and r=-0.24 in women, p<0.00001), and iv) lower in subjects with metabolic syndrome (MetS) than in the absence of MetS (1.82 [1.70, 1.95] ng/mL vs. 2.11 [2.06, 2.16] ng/mL, p=0.021). CONCLUSIONS: We defined the normal range of plasma PTX3 in healthy Japanese subjects, and also showed the relationship between plasma PTX3 levels and established coronary risk factors, including MetS. PTX3 could be an ideal biomarker because it is a marker relatively independent from established coronary risk factors.

Plasma Pentraxin3 is a novel marker for nonalcoholic steatohepatitis (NASH).

BACKGROUND: The changes in the liver in nonalcoholic fatty liver disease (NAFLD) range over a wide spectrum, extending from steatosis to steatohepatitis (NASH). However it has remained difficult to differentiate between NASH and non-progressive NAFLD on the basis of the clinical findings alone. AIMS: In this study we investigated the clinical usefulness of plasma Pentraxin3 (PTX3) levels to predict NASH. Plasma PTX3 was measured in 70 patients with histologically verified NAFLD (28 with non-NASH and 42 with NASH) and 10 healthy control subjects. RESULTS: The plasma PTX3 level was significantly higher in the NASH cases than in the non-NASH cases (p = 0.0021) and control subjects (p = 0.045). And the plasma PTX3 level was significantly higher in the stages 3-4 NAFLD cases than in the stages 0-2 NAFLD cases (p < 0.0001). The PTX3 values were closely correlated with the stages of liver fibrosis (p < 0.0001, Kruskal-Wallis test). To detect NASH compared with non-NASH, the area under the curve for plasma PTX3 were 0.755, and to detect stages 3-4 NAFLD compared with stages 0-2 NAFLD, the area under the curve for plasma PTX3 were 0.850. CONCLUSION: This is the first study to demonstrate consistent and profound elevation of plasma PTX3 levels in NASH in comparison with non-NASH. The results suggest that plasma PTX3 levels may not only be laboratory values that differentiate NASH from non-NASH, but marker of the severity of hepatic fibrosis in NASH.

Pentraxin 3, a new marker for vascular inflammation, predicts adverse clinical outcomes in patients with heart failure.

BACKGROUND: Pentraxin 3 (PTX3) is a novel inflammatory marker produced by endothelial cells, smooth muscle cells, and macrophages. The purpose of the present study was to examine the clinical significance of plasma PTX3 levels in patients with heart failure. METHODS: We measured the plasma PTX3 levels in 196 patients with heart failure and 60 control subjects without heart failure by sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 655 days with the end points of cardiac death or progressive heart failure requiring rehospitalization. RESULTS: Plasma PTX3 concentrations were higher in patients with heart failure than in control subjects (P < .0001) and increased as the severity of New York Heart Association functional class advanced (P < .0001). A total of 63 cardiac events occurred during a follow-up period, and cardiac event-free rate was markedly lower in patients with high PTX3 levels than in those with normal PTX3 levels (44.7% vs 89.2%, P < .0001). The multivariate Cox proportional hazard analysis demonstrated that the plasma PTX3 level, but not the high-sensitive C-reactive protein, was the independent predictor of cardiac events (hazard ratio 1.20, 95% CI 1.03-1.40, P = .0162). Patients were divided into 4 groups based on plasma PTX3 values from first to fourth quartile. The highest fourth quartile of plasma PTX3 levels was associated with the highest risk of cardiac events (9.23-fold compared with the first quartile). CONCLUSIONS: The plasma PTX3 level provides important prognostic information for the risk stratification of patients with heart failure.

Increased expression of long pentraxin PTX3 in inflammatory bowel diseases.

The aims of this study were to investigate the expression of pentraxin-3 in inflamed gastrointestinal tissue in patients with inflammatory bowel diseases and to elucidate the usefulness of plasma pentraxin-3 level as an inflammation marker in patients with inflammatory bowel diseases. Pentraxin-3 immunoreactivity was found in infiltrating neutrophils and vessels in the inflamed gut. Plasma pentraxin-3 concentration in patients with active inflammatory bowel diseases was significantly higher than that of normal subjects and patients with inactive inflammatory bowel diseases. Significant positive correlations of clinical disease activity with plasma pentraxin-3 concentration and serum CRP concentration were found in patients with inflammatory bowel diseases. Pentraxin-3 is directly produced from the inflamed gut in inflammatory bowel diseases. In conclusion, plasma pentraxin-3 concentration is a useful marker for understanding the disease activity in patients with inflammatory bowel diseases.

Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages.

Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by various cells, such as monocytes/macrophages (Mphis) in response to lipopolysaccharide (LPS) and proinflammatory signals. We performed immunoblotting, immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) of PTX3 in human monocyte-derived Mphis and neutrophils. PTX3 expression was observed in the cytoplasm of both GM-CSF induced monocyte-derived Mphi (GM-Mphi) and M-CSF induced monocyte-derived Mphi (M-Mphi). PTX3 level in both Mphis was up-regulated at 24 h after LPS stimulation. Moreover, we confirmed PTX3 expression in freshly isolated neutrophils, and PTX3 level was distinctly up-regulated at 6 and 24 h after LPS stimulation. These findings suggested that PTX3 expression, not only in Mphis, but also in neutrophils, may reflect the role of PTX3 in inflammation. We believe that PTX3 can contribute as a diagnostic tool to evaluate inflammation at peripheral sites.

Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.

OBJECTIVE: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed. METHODS AND RESULTS: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group. CONCLUSIONS: The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.