Biomarkers Of Remodeling Research Articles

Osteopontin in Vascular Calcification: A Central Player or Accidental Witness?

Osteopontin (OPN) is an integrin-binding ligand belonged to the family of N-linked glycoprotein, which is produced by activated mononuclears and linking systemic inflammation, atherosclerosis, and vascular remodeling. There is a large body of evidence regarding the controversial role of OPN in vascular calcification, while OPN is considered a pretty accurate biomarker of vascular remodeling with promising predictive value for cardiovascular (CV) disease and CV events. The short communication depicts the discussion about some controversies regarding exclusive role of OPN in several phases of vascular remodeling.

Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients.

Background Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. Aim To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. Method We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Results Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. Conclusion ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.

Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment

Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming.Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy.Results S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r2=0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID).Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology.

Depleted Leukocyte Mitochondrial DNA Copy Number Correlates With Unfavorable Left Ventricular Volumetric and Spherical Shape Remodeling in Acute Myocardial Infarction After Primary Angioplasty.

Left ventricular (LV) shape influences LV systolic function. It is possible to assess LV shape using 3-D echocardiography sphericity index (SI). Maintaining mitochondrial DNA copy number (MCN) is important for preserving mitochondrial function and LV systolic function after acute myocardial infarction (AMI). Information is limited, however, regarding the relationship between leukocyte MCN and the subsequent change in LV shape after AMI. Fifty-five AMI patients undergoing primary angioplasty were recruited. Plasma MCN was measured before primary angioplasty using quantitative polymerase chain reaction. 3-D echocardiography measurement of SI was performed at baseline, and at 1-, 3-, and 6-month follow-up. AMI subjects with MCN lower than the median had a higher 6-month SI and LV volume compared with those with higher MCN. Baseline echocardiographic parameters were similar between the 2 groups. MCN was negatively correlated with 3- and 6-month SI, and 3- and 6-month LV volume. On multiple linear regression analysis, baseline plasma MCN could predict LV SI and LV volume at 6 months after primary angioplasty for AMI, even after adjusting for traditional prognostic factors. In AMI patients, higher plasma leukocyte MCN at baseline was associated with favorable LV shape and remodeling at 6-month follow-up. Plasma leukocyte MCN may provide a novel prognostic biomarker for LV remodeling after AMI.

Detection of molecular biomarkers as a diagnostic tool in the planning and progression of orthodontic treatment

Orthodontic treatment focuses on providing patient care at the appropriate timing to utilize the growth potential for best results. It involves growth modification of the craniofacial region along with alveolar bone remodeling during tooth movement. The dynamic process of bone metabolism involves the release of biochemical mediators in the circulation. These molecules are indicative of the bone remodeling activity of osteoblastic deposition and osteoclastic resorption. Such biomarkers when detectable in the systemic circulation highlight the skeletal maturity of orthodontic patients and when detected locally as, in gingival crevicular fluid (GCF) and saliva, indicate the progression of orthodontically induced alveolar bone remodeling. Assessment of molecular biomarkers of bone remodeling in the body fluids would aid the clinicians in planning orthodontic treatment at the ideal timing and evaluating the advent of the treatment.

Galectin-3, a marker of cardiac remodeling, is inversely related to serum levels of marine omega-3 fatty acids. A cross-sectional study.

ObjectiveMarine polyunsaturated n-3 fatty acids (n-3 PUFA) may have cardioprotective effects and beneficial influence on the fibrotic process. We evaluated the associations between serum marine n-3 PUFA and selected biomarkers of fibrosis and cardiac remodeling in elderly patients with acute myocardial infarction.SettingFrom the ongoing OMega-3 fatty acids in Elderly patients with Myocardial Infarction (OMEMI) trial, 299 patients were investigated. Soluble ST2 (sST2), Galectin-3 (Gal-3) and the serum content of major marine n-3 and n-6 PUFA were analyzed 2–8 weeks after the index acute myocardial infarction.ResultsGal-3 was inversely correlated to eicosapentaenoic acid (r = −.120, p = .039) and docosahexaenoic acid (r = −.125, p = .031) and positively correlated to the n-6/n-3 ratio (r = .131, p = .023). Gal-3 levels were significantly higher in diabetics vs non-diabetics (12.00 vs 9.61 ng/mL, p = .007) and in patients with NYHA class ≥III for dyspnea at inclusion (11.33 vs 9.75 ng/mL, p = .006).ConclusionsThe associations between the marine n-3 PUFA and levels of Gal-3 indicate beneficial effects of n-3 PUFA on cardiac remodeling in an elderly population with acute myocardial infarction.

Anti-inflammatory activity of Juniper (Juniperus communis) berry essential oil in human dermal fibroblasts

Although juniper (Juniperus communis) berry essential oil (JEO) has been used in skin care products, research on its biological activity in human skin cells is scarce. In the current study, we explored the biological activity of JEO (with alpha-pinene as the major active component) in pre-inflamed human dermal fibroblasts, which were designed to mimic the disease biology of chronic inflammation and fibrosis. We analyzed the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. JEO exhibited robust antiproliferative activity and significantly inhibited the increased production of the proinflammatory chemokines interferon gamma-induced protein 10 (IP-10) and interferon-inducible T-cell alpha chemoattractant (I-TAC). Additionally, JEO significantly inhibited tissue remodeling biomarkers, namely collagen I, collagen III, and plasminogen activator inhibitor 1 (PAI-I). Macrophage colony-stimulating factor (M-CSF), an immunomodulatory protein molecule, was also significantly downregulated by JEO. Moreover, we found that JEO robustly modulated global gene expression. Ingenuity Pathway Analysis also showed that JEO affected many important signaling pathways that are closely related to metabolism, inflammation, immune response, wound healing, and cancer biology. This study provides the first evidence of the biological activity of JEO in human dermal fibroblasts. Thus, JEO is a promising therapeutic candidate for inflammatory conditions in the skin.

Phytochemical Pharmacokinetics and Bioactivity of Oat and Barley Flour: A Randomized Crossover Trial.

While dietary fiber plays an important role in the health benefits associated with whole grain consumption, other ingredients concentrated in the outer bran layer, including alkylresorcinols, lignans, phenolic acids, phytosterols, and tocols, may also contribute to these outcomes. To determine the acute bioavailability and pharmacokinetics of the major phytochemicals found in barley and oats, we conducted a randomized, three-way crossover trial in 13 healthy subjects, aged 40–70 years with a body mass index (BMI) of 27–35.9 kg/m2. After a two-day run-in period following a diet low in phytochemicals, subjects were randomized to receive muffins made with either 48 g whole oat flour, whole barley flour, or refined wheat flour plus cellulose (control), with a one-week washout period between each intervention. At the same time, an oral glucose tolerance test was administered. In addition to plasma phytochemical concentrations, glucose and insulin responses, biomarkers of antioxidant activity, lipid peroxidation, inflammation, and vascular remodeling were determined over a 24-h period. There was no significant effect on acute bioavailability or pharmacokinetics of major phytochemicals. Administered concurrently with a glucose bolus, the source of whole grains did not attenuate the post-prandial response of markers of glucoregulation and insulin sensitivity, inflammation, nor vascular remodeling compared to the refined grain control. No significant differences were observed in the bioavailability or postprandial effects between whole-oat and whole-barley compared to a refined wheat control when administered with a glucose challenge. These null results may be due, in part, to the inclusion criteria for the subjects, dose of the whole grains, and concurrent acute administration of the whole grains with the glucose bolus.

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis

The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, includingage, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Factor IX-Deficient Mice Have Decreased Skeletal Health

Background:We have previously shown that factor VIII deficiency decreases skeletal health in persons with hemophilia and animal mouse models; however, it is uncertain if this is unique to factor VIII deficiency or persists in factor IX (FIX) deficiency as well. Animal models can eliminate genetic and environmental factors of a complex trait like osteoporosis, and offer more invasive testing beyond bone mass density (BMD), studying bone properties using microtomography (μCT), histomorphometry and biomechanics. Decreased skeletal health can be caused by altered signaling between cells that are responsible for bone remodeling, osteoblasts (build bone) and osteoclasts (absorb bone). Understanding mechanisms of bone disease present in factor deficient mice can impact clinically how it is diagnosed and treated in the future.Methods:FIX-deficient and wild-type (WT) littermates were scanned using peripheral dual energy X-ray absorptiometry (DEXA) to obtain measurements for whole body BMD and femoral BMD at 10 and 20 weeks of age. Cortical bone at the midshaft of the femur was analyzed using microtomography (μCT) and biomechanical testing determined by three-point bending. Three-dimensional high resolution μCT analysis of a tibia is analyzed for bone histomorphometry. Important biomarkers of bone remodeling are analyzed on collected mouse serum and include measuring alkaline phosphatase (ALP) activity spectrophotometrically, osteoprotegrin (OPG), receptor activator of nuclear factor kappa-B Ligand (RANKL) and osteocalcin by commercially available ELISA kits.Results:FIX-deficient mice have decreased skeletal health compared to their wild-type (WT) littermate controls at both 10 and 20 weeks of age, without statistical differences in weight or body length.At 10 weeks, FIX-deficient mice (n=11) have lower whole body BMD (p=0.006) and femoral BMD (p=0.015) compared to WT littermates (n=12). Femoral μCT analysis shows parameters related to bone size, including cortical area (p=0.078) and marrow area (p=0.001) are decreased, and overall cross-sectional area (p=0.002). Three-point bending of the bones have decreased in ultimate failure (p=0.042) and stiffness (p=0.039). High resolution μCT of the tibia show decreased total bone volume (p=0.004) and at the midshaft the cortical bone (p=0.004), marrow area (p=0.029), and the total area (p=0.004).At 20 weeks, FIX-deficient mice (n=14) show decreased whole body BMD (p=0.044) and femoral BMD (p=0.053) trends from their WT littermates (n=15). Femoral μCT analysis shows decreased cortical area (p=0.038). Ultimate failure (p=0.053) and stiffness (p=0.002) differences are present in this group. No differences in cortical bone are seen with high resolution μCT, but do have distinct decreased cancellous bone in the tibia's metaphysis. The FIX-deficient bones show decreased bone volume (p=0.05) and structural differences with decreased trabecular number (p=0.03) and trabecular connectivity (p=0.01), and increased trabecular space (p=0.03).Receptor activator of nuclear factor kappa-B ligand (RANKL) located on osteoblasts plays a direct role in bone metabolism with osteoclasts, by binding to RANK causing precursor osteoclasts to mature and begin bone resorption. At 10 weeks of age RANKL was not detectable in our assays. At 20 weeks of age, RANKL was found to be significantly decreased in FIX-deficient mice over WT littermates (p=2.2E-06).OPG is a receptor decoy that inhibits bone resorption by binding to RANKL on osteoblasts. At 10 weeks, the FIX-deficient mice were found to have lower levels of OPG compared to WT controls (p=0.012); however, at 20 weeks, there was a marked increase in OPG levels of the FIX-deficient mice (p=5.7E-05). Bone building biomarkers, ALP activity and osteocalcin showed no measurable differences in serum at 10 or 20 weeks of age (p>0.5) and (p>0.2) respectively.Conclusions:FIX deficent mice have bone disease suggesting that alteration of the clotting cascade has a direct impact on skeltal health. The mechanism behind of how factor deficiency alters bone health is unclear, but the RANKL/OPG data is consistent with aberrant osteoblast-osteoclast signaling. Our laboratory is actively investigating the mechanism of decreased skeletal health associated with factor deficiencies. DisclosuresTaylor:CSL Behring: Consultancy, Research Funding; Kedrion: Research Funding; Baxalta/Shire: Consultancy, Research Funding; Novo Nordisk: Research Funding.

Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes.

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.

Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy.

HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+, n = 72) and HIV-seronegative (HIV-, n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (ie, angiopoietin 2, Tie-2, and vascular endothelial growth factor, VEGF) were collected. HIV+ and HIV- participants had similar levels of plasma angiopoietin 2 (P = 0.48), Tie-2 (P = 0.27), VEGF (P = 0.18), and PP (P = 0.98). In a multivariable regression model, HIV interacted with Tie-2 (β = 0.41, P < 0.01) and VEGF (β = -0.43, P = 0.01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = 0.31, P < 0.01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = -0.33, P = 0.01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function.

Abstract 11916: Circulating Concentrations of Orexin A Predict Left Ventricular Myocardial Remodeling

Introduction: Left ventricular reverse remodeling (LVRR) may occur with guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF); LVRR is associated with better outcome in this setting. Molecular factors predictive of LVRR are not well understood. Background: Recent data suggest the minor allele for rs7767652 (upstream to the hypocretin/orexin receptor-2 [ HCRTR2 ] gene) is inversely associated with likelihood for LVRR after GDMT. Infusion of orexin A (the HCRTR2 receptor ligand) was protective against LV remodeling. Hypothesis: Concentrations of circulating orexin A predict LV remodeling in HFrEF (left ventricular ejection fraction [LVEF] &lt;40%) patients treated with GDMT. Methods: We measured concentrations of orexin A in 113 HFrEF patients at baseline and at 10 months. Patients underwent echocardiography at the same time points. Measures of LV remodeling included LV end-diastolic and end-systolic volume index (LVEDVi, LVESVi) and LVEF. Results: As a function of the median baseline orexin A concentration of 1.04 ng/mL, there was no difference between groups in baseline characteristics, and no difference in concentrations of other prognostic biomarkers. Subjects with baseline orexin A ≥ 1.04 ng/mL had significantly greater reduction in LVEDVi and LVESVi and a trend towards greater improvement in LVEF at 10 months. Significantly fewer subjects with a baseline Orexin A concentration ≥ 1.04 ng/mL had increase in LVEDVi or LVESVi at study completion ( Table ). In binomial regression adjusted for age, gender, and baseline LV volumes, subjects with a baseline orexin A ≥ 1.04 ng/mL were less likely to have increase in LVEDVi (relative risk [RR] 0.51; 95% confidence interval [CI]: 0.30-0.84, P = 0.007) or LVESVi (RR 0.49; 95% CI: 0.28-0.85, P = 0.01). Follow up orexin concentrations did not add to baseline values for predicting LVRR. Conclusions: Orexin A is a unique prognostic biomarker for myocardial remodeling in chronic HFrEF.

Assessment of CardiOvascular Remodelling following Endovascular aortic repair through imaging and computation: the CORE prospective observational cohort study protocol

IntroductionThoracic aortic stent grafts are orders of magnitude stiffer than the native aorta. These devices have been associated with acute hypertension, elevated pulse pressure, cardiac remodelling and reduced coronary perfusion....

Biomarkers of apoptosis, inflammation, and cardiac extracellular matrix remodelling in the prognosis of heart failure.

Biomarkers of apoptosis, inflammation, and cardiac extracellular matrix remodelling in the prognosis of heart failure.

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD – results from the ECLIPSE study

BackgroundThere is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortality in COPD and measured neo-epitopes originating from ECM proteins associated with lung tissue remodeling.MethodsBiomarkers of ECM remodeling were assessed in a subpopulation (n = 1000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort. Validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, III, IV, and VI, elastin, and biglycan, and formation of collagen type VI as well as fibrinogen and C-reactive protein were used. Multivariate models were used to assess the prognostic value of these biomarkers.ResultsThirty subjects (3.0 %) died during follow-up. Non-survivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers. All collagen biomarkers were significantly elevated in non-survivors compared to survivors. Mortality risk was significantly increased for subjects with collagen remodeling biomarkers in the upper quartile, especially for the degradation fragment of collagen type IV C6M (hazard ratio 6.6 [95 % confidence interval 2.9-15.2], P < 0.0001) after adjusting for relevant confounders.ConclusionsSerological biomarkers of collagen remodeling were strongly associated with mortality in subjects with COPD indicating that assessment of tissue turnover in the parenchyma and small airways may be useful in the prognosis of COPD.Trial registration NCT00292552, GSK Study No. SCO104960.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0440-6) contains supplementary material, which is available to authorized users.

Differential association of plasma monocyte chemoattractant protein-1 with systemic inflammatory and airway remodeling biomarkers in type-2 diabetic patients with and without asthma.

BackgroundChronic inflammation is a hallmark of type-2 diabetes (T2D) and asthma. Monocyte chemoattractant protein (MCP)-1 or CCL-2 is a key regulator of monocytic infiltration into the sites of inflammation. The changes in systemic MCP-1 levels and its relationship with other inflammatory/immune markers in T2D patients with asthma remain unclear and have been addressed in this study.MethodsPlasma samples from 10 asthmatic T2D patients (Group I: BMI = 37.82 ± 9.75 kg/m2), 13 non-asthmatic T2D patients (Group II: BMI = 32.68 ± 4.63 kg/m2), 23 asthma patients without T2D (Group III: BMI = 30.14 ± 6.74 kg/m2), and 25 non-asthmatic non-diabetic controls (Group IV: BMI = 27.99 ± 5.86 kg/m2) were used to measure levels of MCP-1 and multiple cytokine/chemokine biomarkers with bead-based multiplex assays using Luminex technology. IgE/ECP were measured using commercial ELISA kits. Data (mean ± SEM) were compared using unpaired Student’s t-test and linear dependence between two variables was assessed by Pearson’s correlation coefficient (r) and P ≤ 0.05 was considered as significant.ResultsPlasma MCP-1 levels were significantly higher in Group I (337.95 ± 46.40 pg/mL) as compared with Group II (216.69 ± 17.30 pg/mL), Group III (251.76 ± 19.80 pg/mL), and Group IV (223.52 ± 133.36 pg/mL). MCP-1 showed differential association with tested biomarkers by correlating positively with: (i) IFN-α2, IL-10, fractalkine, and VEGF in T2D patients with asthma; (ii) IL-6 and GRO-α in T2D patients without asthma; (iii) MDC, IP-10, GM-CSF, FGF-2, and PDGF-AA/BB in patients with asthma only; and (iv) FPG and TG in non-asthmatic non-diabetic controls. MCP-1 associated with IL-1RA only in subjects with asthma.ConclusionThe systemic MCP-1 levels were significantly elevated in T2D patients with asthma as compared with those without asthma and/or diabetes while these changes correlated differentially with important biomarkers of inflammation and airway remodeling.

Serum Galectin-3 Levels Predict Recurrences after Ablation of Atrial Fibrillation.

Galectin-3 is a biomarker of fibrosis and atrial remodeling, involved in the mechanisms of initiation and maintenance of atrial fibrillation (AF). We sought to study the accuracy of galectin-3 level in predicting recurrences of AF after ablation. Serum concentrations of galectin-3 were determined in a consecutive series of patients addressed for AF ablation in our center. After a 3-month blanking period, recurrences of atrial arrhythmias were collected during the first year in all patients, using Holter monitoring at 3, 6 months and 12 months. A total of 160 patients were included, with a mean galectin-3 rate was 14.4 ± 5.6 ng/mL. At 12-month, 55 patients (34%) had reexperienced sustained atrial arrhythmia. Only higher galectin-3 level (HR = 1.07 [1.01–1.12], p = 0.02) and larger left atrial diameter (HR = 1.07 [1.03–1.12], p = 0.001) independently predicted recurrence. Patients with both galectin-3 level <15 ng/mL and left atrial diameter <40 millimeters had a 1-year arrhythmia-free survival rate − after a single procedure without anti-arrhythmic drug − of 91%, as compared with 41% in patients with galectin-3 ≥ 15 and left trial diameter ≥40 (p < 0.0001), whether AF was paroxysmal or persistent. Galectin-3 and left atrial diameters, rather than clinical presentation of AF, predict recurrences after ablation.

Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

ObjectivesChronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been associated with exacerbations of COPD. However, characterization of these in individuals with clinically stable COPD is lacking. The aim of this study was to characterize the collagen remodeling in stable COPD by the serological assessment of neo-epitopes. Design and methodsSixty-eight subjects with clinically stable COPD were included into the study at baseline, and 27 came back for a four weeks follow-up visit. Serum and plasma levels of neo-epitopes were assessed for the evaluation of collagen type III (C3M), IV (C4M, C4Ma3, P4NP 7S), and VI (C6M, Pro-C6) remodeling. ResultsC3M, C4M, C4Ma3, P4NP 7S, and C6M levels were significantly elevated in COPD subjects compared with healthy controls (p<0.0001 to p=0.044). Each neo-epitope biomarker was significantly correlated between serum and plasma (p<0.0001) and most biomarkers were stable in the majority of patients from baseline to week four. Serum C6M levels were weakly correlated with FEV1% predicted (r=−0.274, p=0.025) and serum Pro-C6 levels were elevated in subjects with previous exacerbations (p=0.014). C3M, C4Ma3, C6M, and P4NP 7S were weakly correlated with MRC dyspnea scores (p<0.01). No associations were seen with BMI, smoking, duration of COPD, blood oxygen saturation, shuttle walk test distance, GOLD grades, or CAT scores. ConclusionsSerological biomarkers of collagen remodeling were elevated in subjects with COPD as compared with healthy individuals. Biomarker levels were significantly correlated with measures of dyspnea, indicating a relationship with degree of symptoms, while only C6M showed a weak but significant association with lung function. Biomarker levels were not related to GOLD grades, which was in line with previous studies indicating that ECM remodeling may be related to disease activity rather than severity.

PP.20.18] CORRELATION OF BIOMARKERS OF CARDIAC REMODELLING, INFLAMMATION AND MYOFIBROSIS WITH PARAMETERS OF CARDIAC STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Several studies showed role of novel biomarkers of cardiac remodelling and myofibrosis in prediction of risk of heart silure in patient with arterial hypertension (AH). Aim of the study was to evaluace relation of biomarkers of cardiac remodelling (NT-proBNP, soluble receptor ST2), marker of inflammation ceruloplasmin and marker of myofibrosis (galectin-3) with parameters of cardiac structure and function as assessed by echocardiography. Design and method: Patients population and methods: group of 64 patients (37 males, 27 females, mean age 64 years) with esential AH underwent laboratory examination and echo study same date in hypertsnion clinic. Biomarkers were assessed by RayBio™ Custom Quantibody Array. Dual mode, Pulse-Doppler and Tissue Doppler Imaging were used for the assessment of: cardiac chambers size, left ventricular (LV) ejection fraction, calculation of LV mass index (LVMI) and RWT (relative wall thickness) assessment of LV diastolic function with E/A (early filling velocity to atral contraction velocity) ratio and E/E [Combining Acute Accent] (early filling to mean mitral annulus motion velocity) ratio. Results: Mean NT-proBNP level was 16.5 pmol/ll, sST2 139,9 pg/ml, galectinu3 1470 pg/ml and ceruloplasminu 200 mg/l. Mean LV EF was 66,8 % (median 66), E/A ratio 0,9 (0,85), E/E [Combining Acute Accent] ratio 6,8 (6,3), LVMI 84,1 (83) g/m2 and RWT 0,40 (0,41). NT-proBNP correlated with ceruloplasmin level only (r = 0,222, but p = 0,08), other correlation between biomarkers were not significant too. NT-proBNP correlated with urea level (r = 0,333, p < 0,01), ceruloplasmin correlated with urea (r = 0,316, p < 0,05) and sST2 correlated with uric acid (0,416, p < 0,05). Concentration of biomarkers did not correlate with echocardiography parameters. Conclusions: Novel biomarkers of cardiac remodelling, inflammation and myofibrosis do not correlate with parameters of cardiac structure and function in patients with arterial hypertension.