Pentraxin 3 Levels Research Articles

The potential diagnostic value of serum pentraxin-3 in hepatocellular carcinoma in Egyptian patients

Background and aimHepatocellular carcinoma (HCC) is considered one of the most common cancers in the world and one of the principal causes of cancer-linked deaths. Therefore, identification of new biomarkers for diagnosis, especially early diagnosis of HCC, is very important. Pentraxin 3 (PTX3) is possibly involved in cancer development, and as regard to liver diseases, plasma PTX3 was implicated to be associated with HCC occurrence. Therefore, this study will determine the serum PTX3 levels in patients with cirrhosis and HCC and to assess the potential diagnostic value in HCC in Egyptian patients.ResultsPentraxin 3 was significantly higher in HCC patients than in cirrhotic patients (p < 0.001); also, serum PTX3 was significantly correlated with number, size of focal lesions, the presence of portal vein thrombosis, and BCLC staging (p < 0.001).ConclusionThe significant increased levels of serum pentraxin 3 in HCC may support its use as an early marker for HCC, either alone or in combination with serum alpha-fetoprotein (AFP), allowing early diagnosis and prompt intervention.

#941 Pentraxin-3 as a marker of coronary artery disease in hemodialysis patients

Abstract Background and Aims Pentraxin-3 (PTX3), a novel inflammatory biomarker, has been recognized as a predictor of cardiovascular events in the general population, including coronary artery disease (CAD). Although PTX3 is elevated in dialysis patients, its potential diagnostic value for the estimation of CAD severity is still insufficiently studied. The aim of this study was to evaluate the association between PTX3 and CAD in hemodialysis patients. Method This cross-sectional study included 60 angina-free chronic hemodialysis patients (60% men, mean age 60 ± 11 years, mean dialysis vintage 26 ± 14 months). Coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) were performed to evaluate CAD burden and stenosis severity, which was defined as significant if obstructing more than 50% of the vessel lumen. PTX3 was quantified using an enzyme-linked immunosorbent assay kit. Results Significant coronary artery stenosis was detected in 24 (40%) patients, of which the majority (17; 70.83%) had one-vessel disease. PTX3 was 194.82 ± 68.58 ng/mL in patients with significant CAD, whereas 83.55 ± 11.89 ng/mL in those without significant coronary artery stenosis (p = 0.028). PTX3 levels tend to increase in patients with CACS higher than 200 Agatston units, however statistically significant difference was not reached (p = 0.504). PTX3 levels correlated with age (p &amp;lt; 0.05) and c-reactive protein (p = 0.007), while negatively correlated with body mass index (p &amp;lt; 0.05). Conclusion PTX3 is significantly increased in hemodialysis patients with coronary artery disease. Further studies should elucidate if including PTX3 as a marker for detecting CAD prior to invasive imaging could improve cardiovascular risk stratification even in angina-free hemodialysis patients.

Silencing DDX3 Attenuates Interleukin-1β-Induced Intervertebral Disc Degeneration Through Inhibiting Pyroptosis.

Intervertebral disc degeneration (IVDD) is a common disorder associated with chronic inflammation and cell death. In this study, an IVDD rat model was created through Interleukin-1β (IL-1β) injection. The degeneration of intervertebral disc tissues was assessed using magnetic resonance imaging (MRI), followed by hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. RNA sequencing was performed to identify differentially expressed genes (DEGs) between the IVDD model and control rats. The expression levels of DEGs (DEAD-box polypeptide 3 (DDX3), lysine-specific demethylase 5D (KDM5D), interferon-induced gene-1 (IFIT1), ribosomal protein S10 (RPS10), tenomodulin (TNMD), and pentraxin 3 (PTX3)) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The regulatory effect of DDX3 on pyroptosis in IL-1β-treated nucleus pulpous (NP) cells was assessed after transfection with siRNA of DDX3. A total of 601 DEGs were identified from the IVDD model rat, and were abundant in extracellular matrix (ECM) organization, ECM-receptor interaction, and inflammatory pathways, including the PI3K-Akt, TNF, and AMPK signaling pathways. DDX3, KDM5D, and IFIT1 levels were notably elevated, whereas RPS10, TNMD, and PTX3 levels were decreased in the IL-1β-induced IVDD rat model. Moreover, silencing DDX3 promoted cell proliferation and abolished IL-1β-induced cell apoptosis and pyroptosis. This study revealed the role of DDX3 in IVDD pyroptosis, providing potential target for IVDD management.

Comparison of Pentraxin-3 in Migraine Patients without Aura and Healthy Controls

Background and Objectives: Migraine is a common cerebrovascular condition marked by one-sided, pulsating headache, which may or may not be accompanied with an aura. Migraine is mostly found in females who are of childbearing age. One of the speculated mechanisms for the pathophysiology of migraine is endothelial dysfunction. A new biomarker of inflammatory disorders, pentraxin-3 is often produced by endothelium injury. In earlier investigations, it was shown that migraine sufferers had elevated levels of pentraxin-3. Our study's objectives were to analyze the serum pentraxin-3 levels in migraine sufferers without aura and healthy controls.Methods: It was a cross-sectional comparative study. This was done at the IMBB Department, University of Lahore, Lahore Pakistan, from March 2020 to April 2022. We took 40 diagnosed migraine cases and 40 healthy controls. Detailed examination was done and proformas were filled by both cases and controls. Serum was collected by each of them and pentraxin-3 values were determined by using specific Elisa kits. SPSS version 22 was used for statistical analysis. For normality of data Shapiro wilk test was used. Mann whiteny U test was used for the comparision of means of pentraxin-3 in migrainers and healthy controls.Results: The data were non-normally distributed after the Shapiro-Wilk Test. The average age of the controls was 25±6.06 years, while that of individuals with migraines was 26±7.78 years. Patients with migraine were mostly women. The majority of the patients had BMI category 18 to 24.5. Patients with migraine had mean pentraxin-3 levels of 145.75 ±157.7 pg/l, compared to 43.65 ±33.01 pg/l in the control group. Median was100.5 in cases and 31.15 in controls. P-value was 0.0001.Conclusion: When compared to the control group, migraine patients had considerably higher blood levels of PTX-3, and no correlations between age, BMI, marital status, smoking history, and usage of preventative medications were found.Key words: migraine, pentraxin-3, endothelial dysfunction, C-reactive protein (CRP),

Plasma pentraxin-3 levels and its role in childhood obesity-Is it anti-inflammatory? A matched group study.

Obesity has been associated with chronic low-grade systemic inflammation. This study aimed to investigate the relationship of pentraxin-3 (PTX-3) with anthropometric measurements, dietary content and physical activity level in children. A matched group study. This study was conducted with 91 children aged 6-17 years, divided into two groups: "non-obese group" (Body Mass Index Standard Deviation Score [BMI SDS] <95th percentile) and "obese group" (BMI SDS ≥95th percentile). Plasma PTX-3 levels. The mean age of 91 children included in the study was 12.34 ± 2.86 years. Plasma PTX-3 levels were significantly higher in obese children (p = .028). No significant correlation was found between BMI SDS and plasma PTX-3 values, but a weak positive correlation was found when physical activity level was controlled (r = .176, p = .049). In addition, it was found that fat mass was a partial mediator of plasma PTX-3 level, and an increase in the amount of subcutaneous adipose tissue negatively affected plasma PTX-3 level. Plasma PTX-3 level showed a weak positive correlation (r = .223, p = .017) with physical activity score and dietary polyunsaturated fatty acid intake, while a weak negative correlation with neutrophil-to-lymphocyte ratio. One unit increase in physical activity score or polyunsaturated fatty acid level caused 0.730 and 2.061 unit increases in plasma PTX-3 level, respectively; while one unit increase in dietary fat intake caused 0.413-unit decrease. There was an indirect relationship between the amount of subcutaneous adipose tissue and PTX-3 level. The results of our study suggested that plasma PTX-3 was associated with lower levels of inflammation in children.

The correlation between pentraxin-3, matrix metalloproteinase-9, and estimated glomerular filtration rate in patients with chronic kidney disease

Background: Chronic kidney disease (CKD) is diagnosed when there is a sustained decrease in the estimated glomerular filtration rate (EGFR) over a period of more than 3 months. While Pentraxin-3 (PTX-3) and Matrix Metalloproteinase-9 (MMP-9) levels increase during the acute phase of the kidney injury, chronic conditions often exhibit alteration in the epithelial mesenchymal transition (EMT).Objectives: This study aimed to elucidate the correlation between serum PTX-3, MMP-9, and eGFR in patients with CKD. Method: Thirty hypertensive patients with CKD stages 3, 4, and 5, aged between 16 and 65 years, were enrolled in the study (15 males and 15 females). Diagnosis of CKD was based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria, utilizing serum creatinine, and CKD-epidemiology Collaboration (CKD-EPI) estimates. Subsequently, serum MMP-9 and PTX-3 levels were quantified. Result: Patients with CKD exhibited significantly higher serum levels of PTX3 and MMP9. Furthermore. a significant negative connection between PTX-3, MMP-9, and EGFR was observed. Additionally, CKD patients displayed a correlation between PTX-3 and MMP-9 concentrations.Conclusion: Plasma levels of PTX-3 and MMP-9 serve as unique, promising, and important markers that contribute to the pathogenesis of CKD.

Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Role of serum pentraxin-3 levels in patients with and without diabetic nephropathy

Role of serum pentraxin-3 levels in patients with and without diabetic nephropathy

Vitamin D3 reduces the symptoms of ovarian hyperstimulation syndrome in mice and inhibits the release of granulosa cell angiogenic factor through pentraxin 3

It has been reported that the effective inhibition of vascular endothelial growth factor (VEGF) can prevent the progression of ovarian hyperstimulation syndrome (OHSS). The present study aimed to investigate the mechanism underlying the effect of vitamin D3 (VD3) on OHSS in mouse models and granulosa cells. The effects of VD3 administration (16 and 24 IU) on ovarian permeability were determined using Evans blue. In addition, ovarian pathology, corpus luteum count, inflammatory responses, and hormone and VEGFA levels were assessed using pathological sections and ELISA. Molecular docking predicted that pentraxin 3 (PTX3) could be a potential target of VD3, and therefore, the effects of human chorionic gonadotropin (hCG) and VD3 as well as PTX3 overexpression on the production and secretion of VEGFA in granulosa cells were also investigated using western blotting and immunofluorescence. Twenty-four IU VD3 significantly reversed the increase in ovarian weight and permeability in mice with OHSS. Additionally, VD3 diminished congestion and the number of corpus luteum in the ovaries and reduced the secretion levels of inflammatory factors and those of estrogen and progesterone. Notably, VD3 downregulated VEGFA and CD31 in ovarian tissues, while the expression levels of PTX3 varied among different groups. Furthermore, VD3 restored the hCG-induced enhanced VEGFA and PTX3 expression levels in granulosa cells, whereas PTX3 overexpression abrogated the VD3-mediated inhibition of VEGFA production and secretion. The present study demonstrated that VD3 could inhibit the release of VEGFA through PTX3, thus supporting the beneficial effects of VD3 administration on ameliorating OHSS symptoms.

Estimation of Serum Levels of Pentraxin 3 in Infants with Congenital Heart Disease for Early Detection of Pulmonary Hypertension

Estimation of Serum Levels of Pentraxin 3 in Infants with Congenital Heart Disease for Early Detection of Pulmonary Hypertension

Pentraxin 3 in Myocarditis: Proof-of-Principle Assessment as a Diagnostic and Prognostic Biomarker.

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, andwith a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

Plasma Levels of Pentraxin 3: A Potential Prognostic Biomarker in Urinary Bladder Cancer Patients.

Urinary bladder cancer (BC) represents a major health issue, and identifying novel biomarkers for early disease detection and outcome prediction is paramount. It has already been established that the immune system plays a role in tumour initiation and progression in which the inflammatory marker pentraxin 3 (PTX3) might be involved, presenting a variety of functions in different cancers. The aim of this study was to investigate whether plasma levels of PTX3 could be used as a biomarker for patients with BC. Plasma levels of PTX3 were determined in 118 BC patients and 50 controls by ELISA. Patients with BC had significantly higher PTX3 levels compared to controls. The value as a diagnostic biomarker is probably limited, however, since no significant difference in PTX3 levels was seen between patients with non-muscle-invasive BC and controls; they were seen only between patients with muscle-invasive disease and controls. However, the potential value of PTX3 as a prognostic biomarker was indicated by significantly higher PTX3 levels in patients who developed metastatic disease during follow-up compared to patients who did not develop metastatic disease. The conclusions from this study are that plasma levels of PTX3 have limited value as a diagnostic biomarker, although they have potential as a prognostic biomarker for patients with BC.

The role of pentraxin 3 and oxidative status in the prognosis of multiple myeloma.

Multiple myeloma (MM) is a bone marrow malignancy characterized by plasma cell proliferation. It was aimed to investigate pentraxin 3 (PTX3) levels, oxidative/antioxidative status, and their correlation in MM. In the study, four groups were established, including newly diagnosed MM (NDMM), MM in remission (Rem-MM), relapsed/refractory MM (RRMM) patients, and a healthy control group. PTX3 levels were measured using enzyme-linked immunosorbent assay, and the total antioxidant status (TAS) and total oxidant status (TOS) were assessed with an autoanalyzer. The oxidative stress index (OSI) was calculated using the formula: OSI (arbitrary unit) = TOS (µmol H2O2 Eq/L)/TAS (mmol Trolox Eq/L) × 100. The study involved comparing PTX3, TAS, TOS, and OSI levels among these four groups. PTX3 levels were significantly elevated in NDMM and RRMM groups compared to controls and the Rem-MM group (NDMM vs control; p < 0.001, NDMM vs Rem-MM; p < 0.001, RRMM vs control; p < 0.001, and RRMM vs Rem-MM; p = 0.006). TAS was higher in NDMM and RRMM groups versus controls (p = 0.009 and p < 0.001, respectively), and TOS was higher in rem-MM group versus NDMM and control groups (p < 0.001 and p = 0.016, respectively). OSI was higher in the Rem-MM group than in NDMM and RRMM groups (p < 0.001 and p = 0.009, respectively). Multivariate analysis confirmed associations between MM groups and PTX3 levels. Receiver operating characteristic analysis revealed high specificity (90%) and sensitivity (79%) for PTX3 in NDMM at a >0.56 ng/mL cut-off value. This study suggests that PTX3 levels may have diagnostic and prognostic potential in MM and its relationship with oxidative stress requires further exploration.

Glucocorticoid use in acute respiratory failure from pulmonary causes and association with early changes in the systemic host immune response

BackgroundGlucocorticoids are commonly used in patients with or at-risk for acute respiratory distress syndrome (ARDS), but optimal use remains unclear despite well-conducted clinical trials. We performed a secondary analysis in patients previously enrolled in the Acute Lung Injury and Biospecimen Repository at the University of Pittsburgh. The primary aim of our study was to investigate early changes in host response biomarkers in response to real-world use of glucocorticoids in patients with acute respiratory failure due to ARDS or at-risk due to a pulmonary insult. Participants had baseline plasma samples obtained on study enrollment and on follow-up 3 to 5 days later to measure markers of innate immunity (IL-6, IL-8, IL-10, TNFr1, ST2, fractalkine), epithelial injury (sRAGE), endothelial injury (angiopoietin-2), and host response to bacterial infections (procalcitonin, pentraxin-3). In our primary analyses, we investigated the effect of receiving glucocorticoids between baseline and follow-up samples on host response biomarkers measured at follow-up by doubly robust inverse probability weighting analysis. In exploratory analyses, we examined associations between glucocorticoid use and previously characterized host response subphenotypes (hyperinflammatory and hypoinflammatory).Results67 of 148 participants (45%) received glucocorticoids between baseline and follow-up samples. Dose and type of glucocorticoids varied. Regimens that used hydrocortisone alone were most common (37%), and median daily dose was equivalent to 40 mg methylprednisolone (interquartile range: 21, 67). Participants who received glucocorticoids were more likely to be female, to be on immunosuppressive therapy at baseline, and to have higher baseline levels of ST-2, fractalkine, IL-10, pentraxin-3, sRAGE, and TNFr1. Glucocorticoid use was associated with decreases in IL-6 and increases in fractalkine. In exploratory analyses, glucocorticoid use was more frequent in participants in the hyperinflammatory subphenotype (58% vs 40%, p = 0.05), and was not associated with subphenotype classification at the follow-up time point (p = 0.16).ConclusionsGlucocorticoid use varied in a cohort of patients with or at-risk for ARDS and was associated with early changes in the systemic host immune response.

Serum pentraxin 3 levels in term neonates with persistent pulmonary hypertension.

Persistent pulmonary hypertension of the neonate (PPHN) is a serious disorder. The long pentraxin 3 (PTX3) plays an important role in angiogenesis, cell proliferation, tissue repair and cell regulation. The present study aims to assess the diagnostic and clinical value of PTX3 in PPHN. The present case-control 60 full-term neonates diagnosed with PPHN by echocardiography within 72 hours of birth. In addition, there were 30 age and sex-matched healthy neonates who served as controls. All participants were subjected to careful history taking and complete clinical examination, Laboratory investigations included complete blood count, C-reactive protein (CRP), blood culture and PTX3 level. Radiological investigations included plain X- ray and two-dimensional transthoracic echocardiography (TTE). Comparison between patients and controls revealed that patients had significantly higher CRP (6.12±2.18 versus 3.69±1.25 mg/dl, p<0.001) and PTX3 levels (2.07±0.67 versus 0.96±0.21, p<0.001) when compared with controls. Patients with associated PDA had significantly higher PTX3 levels when compared with patients without (2.58±0.5 versus 2.02±0.51 ng/ml, p = 0.002). Also, patients with associated PFO had significantly higher PTX3 levels when compared with patients without (2.12±1.05 versus 2.05±0.46, p = 0.002). ROC curve analysis identified good performance of CRP and PTX3 levels in diagnosis of PPHN with PTX3 showing better performance. There is a significant association between serum PTX3 levels and PPHN particularly those with associated PDA or PFO.

Diagnostic and Prognostic Value of Pentraxin 3, Interleukin-6, CRP, and Procalcitonin Levels in Patients with Sepsis and Septic Shock.

In this prospective study, we aim to evaluate the effects of antibiotherapy on pentraxin-3 (PTX3), C-reactive protein (CRP), and interleukin-6 (IL-6) levels in patients with sepsis and septic shock. In our study, CRP, procalcitonin, IL-6, and PTX3 levels at initial and 48 hours of the antibiotherapy of patients who were admitted to the pediatric intensive care unit (PICU) with the diagnosis of sepsis and septic shock between June 2020 and March 2021 were compared. Patients were compared with the age-appropriate case-control group formed from the patients who received pre-operative routines to investigate the diagnostic value. CRP, IL-6, and PTX3 levels of the patients were significantly higher compared to controls (P < 0.05). After the 48th hour of treatment compared to initial CRP, lactate and PCT levels were significantly lower (P < 0.05). The IL-6 and PCT levels were significantly higher in patients with mortality than in surviving patients. Surviving patients showed a significant decrease in CRP level at the 48th hour. IL-6 levels of patients with septic shock were significantly higher than those with sepsis (P = 0.010; P < 0.05). In the diagnosis of septic shock, the area under curve was 0.785 for IL-6 and the standard deviation was 0.09 (P = 0.002, cut-off value, >32 pg/mL, 88.9% sensitivity, 65.6% specifity). The results of this study indicated that IL-6 level is an appropriate biomarker with high specificity in the diagnosis of sepsis and septic shock and in evaluating the response to treatment and determining the prognosis.

Effects of Spirulina supplementation in patients with ulcerative colitis: a double-blind, placebo-controlled randomized trial

AimWe conducted a randomized placebo-controlled trial to assess the efficacy of Spirulina (SP) supplementation on disease activity, health-related quality of life, antioxidant status, and serum pentraxin 3 (PTX-3) levels in patients with ulcerative colitis (UC).MethodsEighty patients with UC were randomly assigned to consume either 1 g/day (two 500 mg capsules/day) of SP (n = 40) or control (n = 40) for 8 weeks. Dietary intakes, physical activity, disease activity, health-related quality of life, antioxidant status, erythrocyte sedimentation rate (ESR), and serum PTX-3 levels were assessed and compared between groups at baseline and post-intervention.ResultsSeventy-three patients (91.3%) completed the trial. We observed increases in serum total antioxidant capacity levels in the SP supplementation group compared to the control group after 8 weeks of intervention (p ≤ 0.001). A within-group comparison indicated a trend towards a higher health-related quality of life score after 8 weeks of taking two different supplements, SP (p < 0.001) and PL (p = 0.012), respectively. However, there were no significant changes in participant’s disease activity score in response to SP administration (p > 0.05). Similarly, changes in ESR and PTX-3 levels were comparable between groups post-intervention (p > 0.05).ConclusionsSP improved antioxidant capacity status and health-related quality of life in patients with UC. Our findings suggest that SP supplementation may be effective as an adjuvant treatment for managing patients with UC. Larger trials with longer interventions periods are required to confirm our findings.

Association Between Dipeptidyl Peptidase-4 Inhibitor Use and Cognitive Functions, Brain-Derived Neurotrophic Factor, and Pentraxin-3 Levels in Patients With Type 2 Diabetes.

Background Diabetes mellitus is an important risk factor for dementia, Alzheimer's disease, and other neurodegenerative diseases. Recent findings have made the relationship between the inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme and cognitive functions an important research topic. Objective This study aimed to evaluate the association between DPP-4 inhibitor use and cognitive functions, serum brain-derived neurotrophic factor (BDNF), and pentraxin-3 (PTX-3) levels in patients with type 2 diabetes, compared with the patients who only use metformin treatment. Design, patients, and methods A total of 50 patients with type 2 diabetes (hemoglobin A1c levels at ≤%7.5) who were under treatment with metformin±DPP-4 inhibitor (n=25) or only metformin (n=25) were included in this cross-sectional study. Serum BDNF and PTX-3 levels were assessed using an enzyme-linked immunosorbent assay.A standardized mini-mental test (sMMSE) was used to evaluate cognitive functions. Results There were no significant differences in the characteristics of the study groups. The mean sMMSE score of the patients receiving DPP-4±metformin treatment was statistically higher when compared with patients receiving only metformin treatment (27.16±1.95 vs. 25.40±3.07; p=0.041). The BDNF levels of the patients receiving DPP-4±metformin treatment were considerably higher than the patients receiving only metformin treatment (394.51±205.66 ng/ml vs. 180.63±297.94 ng/ml; p=0.001). The difference in PTX-3 levels between study groups was not statistically significant (5.47±3.44 vs. 3.79±2.53; p=0.055). Conclusion When compared to metformin alone, the use of DPP-4 inhibitors in the treatment of patients with type 2 diabetes was associated with increased serum BDNF levels and improved cognitive functions.

Is atrial fibrillation in HFpEF a distinct phenotype? Insights from multiparametric MRI and circulating biomarkers

BackgroundHeart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently co-exist. There is a limited understanding on whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics. We aimed to determine if patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) represent a distinct phenotype.MethodsIn this secondary analysis of adults with HFpEF (NCT03050593), participants were comprehensively phenotyped with stress cardiac MRI, echocardiography and plasma fibroinflammatory biomarkers, and were followed for the composite endpoint (HF hospitalisation or death) at a median of 8.5 years. Those with AF were compared to sinus rhythm (SR) and unsupervised cluster analysis was performed to explore possible phenotypes.Results136 subjects were included (SR = 75, AF = 61). The AF group was older (76 ± 8 vs. 70 ± 10 years) with less diabetes (36% vs. 61%) compared to the SR group and had higher left atrial (LA) volumes (61 ± 30 vs. 39 ± 15 mL/m2, p < 0.001), lower LA ejection fraction (EF) (31 ± 15 vs. 51 ± 12%, p < 0.001), worse left ventricular (LV) systolic function (LVEF 63 ± 8 vs. 68 ± 8%, p = 0.002; global longitudinal strain 13.6 ± 2.9 vs. 14.7 ± 2.4%, p = 0.003) but higher LV peak early diastolic strain rates (0.73 ± 0.28 vs. 0.53 ± 0.17 1/s, p < 0.001). The AF group had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP, angiopoietin-2 and pentraxin-3, but lower level of interleukin-8. No difference in clinical outcomes was observed between the groups. Three distinct clusters were identified with the poorest outcomes (Log-rank p = 0.029) in cluster 2 (hypertensive and fibroinflammatory) which had equal representation of SR and AF.ConclusionsPresence of AF in HFpEF is associated with cardiac structural and functional changes together with altered expression of several fibro-inflammatory biomarkers. Distinct phenotypes exist in HFpEF which may have differing clinical outcomes.

Abstract TP300: Apolipoprotein-E Deficiency and High Fat Diet Alter Immunomodulatory Cellular and Molecular Determinants Promoting Atherosclerosis, a Stroke Risk Factor

Background: Most ischemic strokes are caused by atherosclerosis. Atherosclerotic plaque formation is modulated by genetic and environmental interactions. Apolipoprotein E (ApoE) regulates lipid metabolism, and its deficiency is associated with dyslipidemia and atherosclerosis. ApoE is abundantly expressed in glial cells and neurons of the brain, affecting the blood brain barrier and cognitive function. Poor dietary habits promote the onset of atherosclerosis. In this study, we examined the effects of ApoE deficiency and high fat diet (HFD) on plaque formation and immunomodulatory cellular and molecular mechanisms in mice models. Methods: Wild type and ApoE knockout (KO) mice were fed with normal or HFD. Carotid plaques were examined using hematoxylin and eosin staining. Targeted proteomic profiling identified the circulating inflammatory proteins. Pathway specific transcriptomic profiles were identified using PCR arrays and real-time PCR. Immunohistochemistry assays were done in brain sections using a neuronal marker (NeuN), an astrocyte marker (GFAP) and a microglia marker (Iba1). The expression of Pentraxin-3 (PTX3), lipocalin2, and PAI-1 were examined using immunohistochemistry. Images were acquired and analyzed using a Keyence fluorescence microscope and NIH ImageJ. Results: ApoE deficiency and HFD enhanced atherosclerotic plaque formation as a function of age in association with a significant increase in circulating pro-inflammatory cytokines in blood/plasma, including M-CSF, C-reactive protein, and PTX3. The number of microglial cells and astrocytes was increased with altered morphology in ApoE KO and aged animals’ brain cortex and dentate gyrus. Whereas neuronal cell number was decreased in the brains of ApoE deficient and aged mice. The mRNA levels of SELE, PAI-1, lipocalin2, and PTX3 were upregulated in ApoE deficient and WT animals fed with HFD. Higher levels of PTX3 were also observed in atherosclerotic plaques. Conclusion: ApoE deficiency and HFD may play a key role in altering immunomodulatory cellular responses and initiating pro-inflammatory molecular signaling. These events may promote atherosclerotic plaque formation, a risk factor for ischemic stroke and worsen brain damage.