<正>阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)诱发炎症和血管损伤,增加心血管疾病(cardio-vascular disease,CVD)的风险,然而OSA造成CVD的机制尚不完全清楚。

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.

BACKGROUNDObstructive 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.METHODSWe 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.RESULTSPentraxin3 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.CONCLUSIONSPlasma 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.

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.

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. Clin Chem Lab Med 2009;47:471-7.

Summary 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.

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.

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.

Long Pentraxin 3 (PTX3) is a newly identified member of the Pentraxin protein family that includes C-reactive protein (CRP). Unlike CRP, PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli. Increased PTX3 levels are found in acute coronary syndromes (ACS). Its role in long-term prediction of clinical outcome is, however, unknown. The aim of the current study was to assess the predictive value of PTX3 concerning all-cause mortality in patients hospitalized for acute chest pain. Plasma PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in blood samples taken on admission in 784 patients admitted for acute chest pain suggestive of ACS. The patients were followed for 24 months concerning clinical outcome. For statistical analysis, the study cohort was divided into quartiles according to PTX3 levels. A multiple logistic regression model was fitted to include standard risk measures. At 24 months follow-up 121 patients had died. By logistic regression, the odds Odds Ratio for death among patients with highest PTX3 levels was 3.13 as compared to those with lowest levels (p=0.007) (table). Long Pentraxin 3 is a new, independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain.

Elevated plasma levels of long pentraxin 3 (PTX3), high-sensitive C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP) are found in acute coronary syndromes (ACS). The aim of this study was to assess the prognostic value of PTX3 as compared to BNP and hsCRP, and their combination, as a prognostic marker of mortality in acute chest pain patients. PTX3 was measured in EDTA plasma with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan). BNP was analysed in EDTA plasma using the Microparticle Enzyme Immunoassay (MEIA) Abbott AxSYM®. HsCRP was measured with the use of an immunoturbidimetric assay (Tinaquant® C-reactive protein (latex) high sensitive assay, Roche Diagnostics). The blood samples were taken on admission in 795 patients. The patients were followed for 24 months concerning mortality. For statistical analysis, the study cohort was divided into quartiles (Q1–4) according to PTX3 levels. A multiple logistic regression was fitted which included standard risk measures. At 24 months follow-up, 121 of the 784 patients included in the model had died. The odds ratio for comparing Q4 versus Q1 for PTX3, BNP and hsCRP were 4.34, 3.35 and 0.52 (p=0.001, p=0.024 and p=0.096), respectively, and the combination of PTX3 and BNP showed an incremental prognostic value (figure ). PTX3 is a new independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain and the combination of this marker with BNP adds substantially to the prognostic value as compared to either marker alone. Figure The number of biomakers greater than the median for % death in 24 months (p<0.001 for comparing the groups)

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.

Backgrounds & Aims: CRP, short pentraxin C-reactive protein, is often used in the evaluation of inflammatory status in ulcerative colitis (UC). However, usually serum CRP level does not increase in active UC because the short pentraxin CRP is produced mainly by the liver in response to interleukin (IL)-6, as well as IL-6 level is not so high in patients with UC. Pentraxin-3 (PTX3) is a prototypic long pentraxin mainly by dendritic cells, macrophages and endothelial cells in response to primary inflammatory stimuli. We reported increased plasma PTX3 concentration in active inflammatory bowel diseases (Kato S et al. Dig Dis Sci 2007 in press). The aims of this study were to investigate the usefulness of plasma PTX3 concentration as an diagnositic and therapeutic marker for patients with UC. Materials & Methods: Plasma PTX3 levels were examined in 46 UC patients by sandwitch ELISA. Mayo Scoring system was used to evaluate disease activity in UC patients. Plasma PTX3 concentrations were evaluated for disease type and clinical course. Sensitivity, specificity and accuracywere evaluated Results: Plasma PTX3 concentration was decreased after treatment for UC. For disease type, plasma PTX3 concentration of total colitis , left side colitis and proctitis type were 8.05+-4.03, 9.22+-5.35 and 3.55+-1.91(concentration of of total colitis , left side colitis vs proctitis type, p<0.05). Serum CRP concentration of of total colitis , left side colitis and proctitis type were 2.01+-3.39, 1.1+-2.71 and 0.11+-0.1. For clinical course, plasma PTX3 concentration of one attack only , relapse-remitting and chronic continuous type were 3.79+-2.52, 8.06+-5.02 and 6.82+-2.93. Serum CRP concentration of one attack only , relapse-remitting and chronic continuous type were 0.12+-0.084, 1.83+-3.43 and 0.57+1.00. Sensitivity, specificity and accuracy of plasma PTX3 concentration against disease activity were 74%, 92% and 83% in UC patients. However, sensitivity, specificity and accuracy of serum CRP concentration were 39%, 100% and 70%. Conclusions: Plasma PTX3 concentration is a good diagnostic and therapeutic marker in patients with UC.