Pentraxin 3 Levels Research Articles

The association between pentraxin 3 in maternal circulation and pathological intrauterine fetal growth restriction

ObjectiveTo assess the diagnostic accuracy of maternal serum pentraxin 3 (PTX3) in identifying pathological intrauterine fetal growth restriction (IUFGR) among women presented in the third trimester of pregnancy with a small for gestational age (SGA) fetus. Study designThis case control study was conducted in Ain-Shams University Maternity Hospital, Abbasiya Square, Cairo, Egypt and included women diagnosed at the third trimester of pregnancy as having a SGA fetus. Cases included pregnant women with pathological IUFGR, while women with physiologically SGA fetus were included in the control group. Diagnosis of antenatal SGA fetus was based on the presence of abdominal circumference <10th percentile. Pathological IUFGR was provisionally diagnosed antenatally by the presence of falling percentiles on serial ultrasound scans and then the definitive diagnosis was established postnatally after comprehensive neonatal evaluation. Maternal venous blood samples were collected from the eligible participants, once at the time of enrollment, to assess serum PTX3 levels using enzyme-linked immunosorbent assay (ELISA). Both groups were then followed up till delivery to confirm the diagnosis. ResultsAmong the 68 pregnant included in the study, PTX3 was found to be significantly elevated in women with SGA fetus due to pathological IUFGR (n=34) than those with physiologically SGA fetus (n=34) [6.5ng/ml (2.5–11.0) versus 1.2ng/ml (0.8–2.5) respectively], with a best cutoff value of ≥1.3ng/ml [sensitivity of 85.3% (95% confidence interval (CI), 68.9–95.0) and a specificity of 73.5% (95% CI, 55.6–87.1)]. Using multivariable binary logistic regression model, amniotic fluid index (AFI) (P=0.010), estimated fetal weight (EFW) (P=0.016), PTX3 level (P=0.041), and umbilical artery pulsatility index (UA-PI) (P=0.027) were all found to be independent diagnostic markers for pathological IUFGR. ConclusionPTX3 is a promising marker that deserves further evaluation as it may differentiate normal and abnormal fetal growth among women presenting at third trimester of pregnancy with a SGA fetus.

Pentraxin 3 is reduced in bipolar disorder.

Immunologic abnormalities have been found in bipolar disorder but pentraxin 3, a marker of innate immunity, has not been studied in this population. Levels of pentraxin 3 were measured in individuals with bipolar disorder, schizophrenia, and non-psychiatric controls. Linear regression models were used to compare the pentraxin 3 levels in each of the psychiatric groups to that in the control group, adjusting for demographic and clinical variables. Logistic regression models were used to calculate the odds ratios associated with levels of pentraxin 3 which differed from specified levels of the control group. The sample consisted of 831 individuals: 256 with bipolar disorder, 309 with schizophrenia, and 266 without a psychiatric disorder. The levels of pentraxin 3 in the bipolar disorder, but not in the schizophrenia, group were significantly lower than those of controls, adjusting for age, gender, race, maternal education, smoking status, and body mass index (t = -3.78, p < 0.001). The individuals with bipolar disorder also had significantly increased odds of having low levels of pentraxin 3 relative to both the 10th and 25th percentile level of the controls and significantly decreased odds of having a level greater than the 75th and the 90th percentile level of the controls, adjusting for the same covariates. Individuals with bipolar disorder have low levels of pentraxin 3 which may reflect impaired innate immunity. An increased understanding of the role of innate immunity in the etiopathogenesis of bipolar disorder might lead to new modalities for the diagnosis and treatment of this disorder.

Abstract 12010: The Pivotal Role of Pentraxin 3, a New Inflammatory Marker, in Hypertensive Failing Heart With Normal Ejection Fraction

Background: Long pentraxin 3 (PTX3) is known to be produced by various types of cell through a lot of inflammatory cytokines such as tumor necrosis factor (TNF)-α. PTX3 is therefore used as an inflammatory marker for acute myocardial infarction and heart failure (HF). However, the precise mechanism of PTX3 in the exacerbation of HF with normal l ejection fraction (HFNEF) remains to be elucidated. Methods: (1) Dahl salt-sensitive hypertensive rats (DS rats), which are the useful model of HFNEF, fed high-salt (HS) DS rats progressively develop hypertension and exhibit LV hypertrophy (LVH) a, followed by HFNEF. In the present study, we used HS loaded DS rats at the age of 15 and 20 weeks to elucidate the mechanism of transition from hypertensive LVH to HFNEF. (2) We examined the levels of PTX3 at the aortic root and the coronary sinus in HFNEF patients who received CAG during the study period. Results: (1) 20-week-old HS loaded DS rats were characterized by prominent LVH and marked LV relaxation abnormality but by the preserved LV systolic function. Compared with control DS rats fed low-salt (LS) diet, LV macrophage infiltration and interstitial fibrosis as shown by histological examination were already significantly increased at the stage of LVH, and remained increased up to the stage of HFNEF (P&lt;0.01). In HS-loaded DS rats suffering from HFNEF, immunoreactivity to PTX3 was similarly localized with cardiac interstitial and perivascular fibrosis, and also expressed in infiltrating macrophages. On the other hand, real-time quantitative RT-PCR showed that cardiac TNF-α and PTX3 mRNA expression was not altered at the stage of LVH, but significantly increased at the stage of HFNEF compared with LS control DS rats, while cardiac transforming growth factor (TGF)-β and CTGF, collagen-related cytokines, significantly increased both at LVH and HFNEF stages. (2) In human, plasma levels of PTX3 at coronary sinus were significantly higher than aortic root in patients with HFNEF (n=11, P&lt;0.01), but not different in normal patients (n=20, P=0.22). Conclusion: PTX3 produced from macrophage, rather than from cardiac fibroblasts, might be associated with transition from LVH to HFNEF. Taken together with human data, PTX3 could be a useful marker for discriminating HFNEF from LVH.

Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder with organ injury related to vasculitis. Inflammation of blood vessels results from auto-immunological activation of endothelial cells. The pentraxin 3 (PTX3), might act as an indicator of vasculitides in many diseases. The aim of this study was to determine whether PTX3 might be useful as a marker of vascular injury in SLE. This study was carried out in a group of 56 SLE women, and in the 28 female volunteers control group. All participants’ plasma and serum samples were collected to estimate concentrations (ELISA) of PTX3, soluble thrombomodulin, soluble E-selectin (sE-selectin), soluble P-selectin (sP-selectin), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble platelet endothelial cell adhesion molecule 1, monocyte chemotactic protein-1 (MCP-1) and von Willebrand factor (vWF) activity. Anthropometric, demographic and lifestyle characteristics of SLE patients were also performed. The SLE patients had higher PTX3, vWF, MCP-1, sE-selectin and sVCAM-1 levels than the controls (1.82 ± 1.56 ng/mL, 237 ± 101%, 70.05 ± 18.31 ng/mL, 111.16 ± 49.15 ng/mL and 978.78 ± 462.35 ng/mL vs. 0.86 ± 0.40 ng/mL, 138 ± 43%, 58.56 ± 13.91 ng/mL, 66.04 ± 27.18 ng/mL and 499.07 ± 125.67 ng/mL, respectively). The independent factors affecting PTX3 expression included Systemic Lupus Erythematosus Disease Activity Index, prednisone dose and anemia severity. Moreover, the PTX3 areas under the curve–receiver operating characteristics curves 0.717 ± 0.056 with cut-off level of 1.96 ng/mL was comparable to vWF, MCP-1, sE-selectin, sP-selectin and sICAM-1. PTX3 and sVCAM-1 were the only factors related to SLE activity. Other vascular injury indicators associated with PTX3 were vWF and sVCAM-1. In conclusion, PTX3 concentrations in SLE patients might serve as a indicator of the activation/dysfunction of vascular endothelium.

Predictors of recurrent cellulitis in five years. Clinical risk factors and the role of PTX3 and CRP

To identify risk factors for recurrence of cellulitis, and to assess the predictive value of pentraxin 3 (PTX3) and C-reactive protein (CRP) measured at baseline. A follow up study of 90 hospitalised patients with acute non-necrotising cellulitis was conducted. Clinical risk factors were assessed and PTX3 and CRP values were measured at baseline. Patients were contacted by phone at a median of 4.6 years after the baseline episode and the medical records were reviewed. Overall, 41% of the patients had a recurrence in the follow up. Of the patients with a history of a previous cellulitis in the baseline study 57% had a recurrence in five year follow up as compared to 26% of those without previous episodes (p=0.003). In multivariate analysis, only the history of previous cellulitis was identified as an independent predicting factor for recurrence. The levels of pentraxin 3 (PTX3) or C-reactive protein (CRP) in the acute phase did not predict recurrence. Risk of recurrence is considerably higher after a recurrent episode than after the first episode. Clinical risk factors predisposing to the first cellulitis episode plausibly predispose also to recurrences.

Systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis.

IntroductionProgression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement.MethodsA cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography.ResultsPatients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6.ConclusionsArterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.

Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats

We aimed to evaluate: (1) endometrial and ovarian tissue injury caused by the glucose toxicity in diabetic rat model and (2) the effect of GLP-1 analog (exenatide) on endometrial and ovarian diabetes induced injury with emphasizing the underlying mechanism. The study group composed of 24 female rats assigned randomly into 3 groups. Group 1 was the control group (n = 8) and received no treatment. Diabetes was induced by intraperitoneal injection of streptozocin for 16 rats which are further assigned randomly into 2 groups: 1 ml/kg intraperitoneal saline was given to Group-2 (diabetic non-treated control group, 8 rats) and 10 µg/kg/day of intraperitoneal exenatide was given to Group 3 (exenatide treated group, 8 rats) for four weeks. After four weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. Diabetes caused endometrial and ovarian tissue injury in rats (p < 0.0001). Serum transforming growth factor beta (TGF-ß), malonylaldehyde (MDA), pentraxin-3 (PTX-3) levels were higher in diabetic rats (p < 0.0001), whereas antimullerian hormone (AMH) was lower (p < 0.001). Serum levels of these markers reflected that Diabetes induced injury in the reproductive tract occured via oxidative stress, fibrosis and severe inflammation. Diabetes diminished ovarian reserve. Exenatide treatment improved the histological degeneration and fibrosis in the endometrium and ovary with concomitant decrease in inflammatory and oxidative stress markers (p < 0.05). Exenatide also improved ovarian reserve (p < 0.05). Glucose toxicity occured severely in ovary and endometrium in DM. After exenatide treatment; ovarian and endometrial injury and fibrosis seems to decrease significantly. The effects of exenatide in rat models give hope to prevent the women with DM from premature ovarian failure and endometrial dysfunction.

The impact of obesity on pentraxin 3 and inflammatory milieu to acute aerobic exercise

Pentraxin 3 (PTX3) has recently been linked to obesity-associated inflammation, serving as a cardioprotective modulator against cardiovascular disease (CVD). Aerobic exercise has been shown to enhance plasma PTX3 levels; however, the impact of obesity on PTX3 response to exercise remains unknown. ObjectiveTherefore, this study sought to examine whether obese subjects would have an attenuated plasma PTX3 response compared to normal-weight subjects following acute aerobic exercise. The relationship of plasma PTX3 with pro-inflammatory cytokines (IL-6 and TNF-α) was also examined. MethodsTwenty healthy subjects (10 obese [4 males and 6 females] and 10 normal-weight [4 males, 6 females]) performed 30min of continuous submaximal aerobic exercise. ResultsAt baseline, obese subjects exhibited approximately 40% lower plasma PTX3 and a 7-fold greater IL-6 concentration compared to normal-weight subjects. In response to exercise, no difference was observed in PTX3 or IL-6 as indicated by area-under-the-curve “with respect to increase” (AUCi) analyses. Furthermore, PTX3 AUCi was positively correlated with cardiorespiratory fitness levels (VO2max) (r=0.594, p=0.006), even after controlling for body mass index. ConclusionThese findings suggest that in addition to obesity-associated complications, low cardiorespiratory fitness levels could impact exercise-induced PTX3 elevations, thereby potentially diminishing PTX3’s effects of anti-inflammation and/or cardioprotection.

Role of Inflammation in Diabetic Macular Edema

Vitreous fluid levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-2, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1 and pentraxin 3 (PTX3) were measured by enzyme-linked immunosorbent assay in 36 patients with diabetic macular edema (DME) and 15 patients with macular hole (MH). Aqueous flare values were measured with a laser flare meter, and macular edema was examined by optical coherence tomography. Vitreous fluid levels of VEGF, sVEGFR-2, sICAM-1, MCP-1 and PTX3 were significantly higher in the patients with DME than in those with MH. There was a significant correlation between the vitreous fluid level of sVEGFR-2 and the levels of sICAM-1, MCP-1 and PTX3. The aqueous flare value was significantly correlated with the vitreous fluid levels of sVEGFR-2, sICAM-1, MCP-1 and PTX3. These findings suggest that inflammatory factors may induce an increase in vascular permeability and disrupt the blood-aqueous barrier in DME patients.

Pentraxin 3 as a Novel Biomarker of Inflammation in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the lungs in which inflammatory markers are involved with significant extrapulmonary effects that may contribute to its severity and complications. Moreover, some of the inflammatory markers such as C-reactive protein (CRP) are associated with COPD. Pentraxin 3 (PTX3) is the member of long pentraxins. The aim of the present study was to investigate the level of PTX3 in patients with COPD. Fifty-four COPD patients and 31 controls were enrolled in this study. Demographical data such as age, sex, cigarette smoking status, comorbidities, drugs, habits, and modified Medical Research Council (MMRC) dyspnea scores were recorded. All patients were asked for COPD Assessment Test™ (CAT). The mean age was 65.7 ± 9.8years, 92% male. Plasma levels of PTX3 were found to be markedly higher in COPD patients [1.65 (0.32-12.72) ng/ml] than in controls [1.05 (0.43-3.26) ng/ml; p = 0.005]. On the other hand, PTX3 values did not differ between COPD stages [A, 1.73 (0.69-11.03); B, 1.49 (0.84-12.52); C, 0.79 (0.52-1.06); and D, 2.09 (0.32-12.72); p = 0.27]. The plasma PTX3 levels were positively correlated with MMRC scores. We conclude that circulating PTX3 levels are elevated in COPD patients. Plasma levels of PTX3 were correlated with dyspnea (MMRC scores). But PTX3 levels were not correlated with the severity of COPD.

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan.

Endometriosis is a common disease in women of reproductive age, and many different treatments have been developed, although none has provided a cure. In this study, the efficacy of losartan, an angiotensin II type 1 receptor blocker and an antiangiogenic and anti-inflammatory agent, on regression of experimental endometriotic implants in a rat model was investigated. Peritoneal endometriosis was surgically induced in 16 mature female Sprague-Dawley rats. The peritoneal endometriotic implant was confirmed after 28 days, and the animals were divided randomly into two groups. The control group (n = 8) was given 4 mL/day tap water by oral gavage, and the losartan group (n = 8) was given 20 mg/kg per day losartan p.o. We compared endometriotic implant size, extent and severity of adhesion, as well as plasma and peritoneal lavage fluid cytokine levels including vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, plasma inflammatory factor pentraxin-3 (PTX-3) and C-reactive protein (CRP) between the treatment groups. Mean surface endometriotic area, histological score of implants, adhesion formation, plasma VEGF, TNF, PTX-3 and CRP levels were significantly lower in the losartan group compared with control (P < 0.05). Furthermore, the peritoneal VEGF level was lower in the losartan group than in the control group (P < 0.001), but peritoneal TNF-α was similar in both groups (P > 0.05). Losartan suppressed the implant surface area of experimental endometriosis in rats and reduced the levels of plasma VEGF, TNF-α, PTX-3 and CRP.

Pentraxin-3 and VEGF in POEMS syndrome: a 2-year longitudinal study.

Circulating Pentraxin 3 (PTX3) and vascular endothelial growth factor (VEGF) levels were measured longitudinally (mean follow-up 2 years) by ELISA in 6 patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome and 16 controls. Expression of PTX3 was also assessed (immunohistochemistry) on sural nerve biopsies from POEMS and vasculitic neuropathy patients. No correlation was found between PTX3 and VEGF levels in POEMS or controls. Sural nerve biopsies from vasculitic neuropathy patients, but not those from POEMS syndrome, showed strong PTX3 staining. PTX3, expression of vessel inflammation/remodeling, and VEGF, crucial pro-angiogenic cytokine, appear to be independently regulated in POEMS syndrome.

Elevated Plasma Level of Pentraxin-3 Predicts In-Hospital and 30-Day Clinical Outcomes in Patients with Non-ST-Segment Elevation Myocardial Infarction Who Have Undergone Percutaneous Coronary Intervention

Objectives: This investigation explored the short-term prognostic value of pentraxin-3 (PTX3) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated by percutaneous coronary intervention (PCI). Methods: We measured plasma levels of PTX3 and other biomarkers in 525 PCI-treated NSTEMI patients (mean age, 57.7 years; 328 males). The associations of PTX3 levels with cardiac events and cardiac deaths occurring within 30 days of discharge were evaluated with multivariable Cox proportional hazard models. Results: Renal function, diabetes prevalence, systolic blood pressure, heart rate and ejection fraction differed significantly in the high PTX3 (≥3.0 ng/ml, n = 107) and low PTX3 (<3.0 ng/ml, n = 418) groups (all p < 0.05). Plasma PTX3 levels were correlated with high-sensitivity C-reactive protein, troponin T and N-terminal pro-B-type natriuretic peptide in NSTEMI patients (all p < 0.05). Kaplan-Meier analysis showed in-hospital and 30-day cardiac events and deaths were higher in the high PTX3 group (both p < 0.01). Elevated PTX3 was an independent predictor of 30-day cardiac events (95% CI 1.09-1.68; p = 0.006) and mortality (95% CI 1.18-2.15; p = 0.002). Conclusions: An elevated plasma level of PTX3 predicts 30-day cardiac events and mortality in PCI-treated NSTEMI patients.

Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study.

IntroductionTimely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia.MethodsWe recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers.ResultsMicrobiologically confirmed pneumonia of bacterial (n =12), viral (n =4) or fungal (n =8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI =0.710 to 0.921, P <0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels ≥1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (β =2.784, SE =0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values ≥1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis.ConclusionsIn this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0562-5) contains supplementary material, which is available to authorized users.

Assessment of the prophylactic role of aspirin and/or clopidogrel on experimentally induced acute myocardial infarction in hypercholesterolemic rats.

IntroductionHyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI).AimThe aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats.MethodsForty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats.ResultsIsoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately.ConclusionCombination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Pentraxin‐3 level at admission is a strong predictor of short‐term mortality in a community‐based hospital setting

The pattern recognition molecule pentraxin-3 (PTX3) is a novel potential marker of prognosis, as elevated levels are associated with both disease severity and mortality in patients with a wide range of conditions. However, the usefulness of PTX3 as a prognostic biomarker in a general hospital setting is unknown. The study cohort consisted of 1326 unselected, consecutive patients (age >40years) admitted to a community hospital in Copenhagen, Denmark. Patients were followed until death or for a median of 11.5years after admission. The main outcome measure was all-cause mortality. Serum samples collected from patients at admission and from 192 healthy control subjects were quantified for PTX3 level by enzyme-linked immunosorbent assay. PTX3 was elevated in patients (median 3.7ngmL(-1) , range 0.5-209.8) compared with healthy nonhospitalized subjects (median 3.5ngmL(-1) , range 0.0-8.3; P=0.0003). Elevated PTX3 levels, defined as above the 95th percentile of the concentration in healthy subjects, were associated with increased overall mortality during the study (P<0.0001). This increase in mortality was greatest in the short term, with an unadjusted hazard ratio (HR) of 6.4 [95% confidence interval (CI) 3.8-11.0] at 28days after admission, compared to 1.7 (95% CI 1.4-2.0) at the end of follow-up. These results were still significant after adjustment for age, gender and glomerular filtration rate: adjusted HR of 5.0 (95% CI 2.9-8.8) and 1.4 (95% CI 1.2-1.8), respectively. These results suggest that PTX3 could be a widely applicable marker of short-term mortality in hospitalized patients and may be useful in the initial risk stratification.

Pentraxin-3 as a prognostic marker in patients with small-cell lung cancer.

The aim of this study was to determine the incidence and role of pentraxin-3 (PTX-3) overexpression as a predictive/prognostic marker in small-cell lung carcinoma (SCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of SCLC. A chart review for demographic and clinical data was performed on patients with SCLC diagnosed between 2005 and 2008. PTX-3 overexpression was evaluated using immunohistochemistry performed on archival paraffin-embedded specimens. 125 patients with SCLC were identified (23 females, 102 males; median age 62.91±8.55 years, range 37-82) all of whom had adequate tissue specimens available for PTX-3 testing. High PTX-3 expression was detected in 25.6% SCLCs and was significantly associated with male gender and smokers. Moreover, elevated PTX-3 levels were correlated with reduced overall (OS) and disease-free survival, and were an independent negative prognostic factor for OS in SCLC. Our findings suggest that high PTX-3 expression appeared to correlate with aggressive behavior in SCLC, and it may be a useful prognostic marker for SCLC patients and a potential molecular target for SCLC treatment.

Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection.

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs)-C reactive protein (hs-CRP) levels in children with severe pulmonary arterial hypertension (PAH) secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Cross sectional study. After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP) and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA) and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43) in the PAH group (group 1) and 0.40±0.72 (0.07-3.45) in group 2. There was a statistically significant difference between the two groups (p<0.01). Serum hs-CRP levels were measured as 2.92±2.12 (0.32-14.7) mg/dL in group 1 and 0.35±0.16 (0.07-3.45) mg/dL in group 2. The hs-CRP level was increased in the PAH group to a significant degree (p<0.01). Our study showed that pentraxin 3 and hs-CRP levels were increased significantly in the PAH group. We consider that inflammation plays an important role in severe pulmonary hypertension and progressive pulmonary arterial hypertension in children with PAH.

Could Pentraxin 3 Be a New Diagnostic Marker for Excessive Inflammatory Response in Cardiac Surgery?

The aim of this study was to compare the dynamics of two inflammatory response biomarkers pentraxin 3 (PTX3) and C-reactive protein (CRP) after cardiac surgery with particular regard to different postoperative clinical manifestation of inflammatory response. In this study, 42 patients undergoing open heart surgery with the use of cardiopulmonary bypass were included and divided in two groups according to the extent of clinical manifestation of inflammatory response: Group A (n=21)-patients with different severity of systemic inflammatory response syndrome (SIRS) and Group B (n=21)-patients with uneventful postoperative period (no SIRS). The serum levels of PTX3 and CRP were evaluated and compared at the following time points: before and at the end of surgery, 6 hours, 1st, 3rd, and 7th day after surgery. The dynamics of CRP levels were comparable between both groups and showed the classical characteristics after cardiac surgery with a peak on the 3rd postoperative day (113 vs. 132 mg/L). In contrast, the dynamics of PTX3 showed an earlier increase of serum levels with the peak on the 1st postoperative day in both groups (36.3 vs. 42.7 ng/mL). Importantly, a significant difference of PTX3 levels was found on the 3rd postoperative day (31.1 vs. 7.0 ng/mL; p<0.006) between the two groups showing significantly delayed decrease of PTX3 levels in patients with SIRS (Group A). This study demonstrates considerably different dynamics of PTX3 levels after cardiac surgery in patients with SIRS and patients without SIRS, thus it may be indicative to start the appropriate therapy.