6 research outputs found

    The role of titin and extracellular matrix remodelling in heart failure with preserved ejection fraction

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    Heart failure with preserved ejection fraction (HFpEF) is characterised by a high incidence of metabolic comorbidities that share the potential to induce both systemic and coronary microvascular inflammation and oxidative stress. These pathophysiological alterations contribute to increased passive stiffness of the myocardium and to diastolic dysfunction, both hallmarks of HFpEF. Passive myocardial stiffness depends mainly on two components: the extracellular matrix (ECM) and the cardiomyocytes. Quantitative and qualitative changes in collagen metabolism leading to myocardial fibrosis determine the ECM-based stiffness of the myocardium. Different noninvasive diagnostic tools to assess myocardial fibrosis are being developed, some of which have demonstrated to correlate with clinical status and prognosis. Cardiomyocytes mainly alter the passive stiffness through alterations in the giant myofilament titin, which serves as a spring. By modifying its phosphorylation state or by direct oxidative effects, titin determines cardiomyocyte-based passive stiffness. Probably the relative importance of cardiomyocyte-based changes is more important in the beginning of the disease, whereas ECM-based changes become more prominent in the more advanced stages. The present review focuses on these changes in ECM and cardiomyocytes in HFpEF and their potential prognostic and therapeutic implications

    Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities

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    Heart failure with preserved ejection fraction (HFpEF) is a complex heterogeneous disease for which our pathophysiological understanding is still limited and specific prevention and treatment strategies are lacking. HFpEF is characterised by diastolic dysfunction and cardiac remodelling (fibrosis, inflammation, and hypertrophy). Recently, microvascular dysfunction and chronic low-grade inflammation have been proposed to participate in HFpEF development. Furthermore, several recent studies demonstrated the occurrence of generalized lymphatic dysfunction in experimental models of risk factors for HFpEF, including obesity, hypercholesterolaemia, type 2 diabetes mellitus (T2DM), hypertension, and aging. Here, we review the evidence for a combined role of coronary (micro)vascular dysfunction and lymphatic vessel alterations in mediating key pathological steps in HFpEF, including reduced cardiac perfusion, chronic low-grade inflammation, and myocardial oedema, and their impact on cardiac metabolic alterations (oxygen and nutrient supply/demand imbalance), fibrosis, and cardiomyocyte stiffness. We focus primarily on HFpEF caused by metabolic risk factors, such as obesity, T2DM, hypertension, and aging

    First thorough identification of factors associated with Cd, Hg and Pb concentrations in mosses sampled in the European Surveys 1990, 1995, 2000 and 2005

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    The aim of this study was, for the first time ever, to thoroughly identify the factors influencing Cd, Hg and Pb concentrations in mosses sampled within the framework of the European Heavy Metals in Mosses Surveys 1990–2005. These investigations can be seen as a follow up of a previous study where only the moss data recorded in the survey 2005 was included in the analysis (Schröder et al. 2010). The analyses of this investigation give a complete overview on the statistical association of Cd, Hg and Pb concentrations in mosses and sampling site-specific and regional characteristics, encompassing data from 4661 (1990), 7301 (1995), 6764 (2000) and 5600 (2005) sampling sites across Europe. From the many metals monitored in the European moss surveys, Cd, Hg and Pb were used as examples, since only for these three metals deposition measurements are being recorded in the framework of the European Monitoring and Evaluation Programme (EMEP). As exemplary case studies revealed that other factors besides atmospheric deposition of metals influence the element concentrations in mosses, the moss datasets of the above mentioned surveys were analysed by means of bivariate statistics and decision tree analysis in order to identify factors influencing metal bioaccumulation. In the analyses we used the metadata recorded during the sampling as well as additional geodata on, e.g., depositions, emissions and land use. Bivariate Spearman correlation analyses showed the highest correlations between Cd and Pb concentrations in mosses and EMEP modelled total deposition data (0.62 ≤ rs ≤ 0.73). For Hg the correlations with all the tested factors were considerably lower (e.g. total deposition r s  ≤ 0.24). Decision tree analyses by means of Classification and Regression Trees (CART) identified the total deposition as the statistically most significant factor for the Cd and Pb concentrations in the mosses in all four monitoring campaigns. For Hg, the most significant factor in 1990 as identified by CART was the distance to the nearest Hg source recorded in the European Pollutant Emission Register, in 1995 and 2000 it was the analytical method, and in 2005 it was the sampled moss species. The strong correlations between the Cd and Pb concentrations in the mosses and the total deposition can be used to calculate deposition maps with a regression kriging approach on the basis of surface maps on the element concentrations in the mosse

    Mosses as biomonitors of atmospheric heavy metal deposition: spatial and temporal trends in Europe

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    In recent decades, mosses have been used successfully as biomonitors of atmospheric deposition of heavy metals. Since 1990, the European moss survey has been repeated at five-yearly intervals. Although spatial patterns were metal-specific, in 2005 the lowest concentrations of metals in mosses were generally found in Scandinavia, the Baltic States and northern parts of the UK; the highest concentrations were generally found in Belgium and south-eastern Europe. The recent decline in emission and subsequent deposition of heavy metals across Europe has resulted in a decrease in the heavy metal concentration in mosses for the majority of metals. Since 1990, the concentration in mosses has declined the most for arsenic, cadmium, iron, lead and vanadium (52–72%), followed by copper, nickel and zinc (20–30%), with no significant reduction being observed for mercury (12% since 1995) and chromium (2%). However, temporal trends were country-specific with sometimes increases being found. Since 1990, heavy metal concentrations in mosses have declined in Europe for most metal

    Poster session 1Cell growth, differentiation and stem cells - Heart72Understanding the metabolism of cardiac progenitor cells: a first step towards controlling their proliferation and differentiation?73Expression of pw1/peg3 identifies a new cardiac adult stem cell population involved in post-myocardial infarction remodeling74Long-term stimulation of iPS-derived cardiomyocytes using optogenetic techniques to promote phenotypic changes in E-C coupling75Benefits of electrical stimulation on differentiation and maturation of cardiomyocytes from human induced pluripotent stem cells76Constitutive beta-adrenoceptor-mediated cAMP production controls spontaneous automaticity of human induced pluripotent stem cell-derived cardiomyocytes77Formation and stability of T-tubules in cardiomyocytes78Identification of miRNAs promoting human cardiomyocyte proliferation by regulating Hippo pathway79A direct comparison of foetal to adult epicardial cell activation reveals distinct differences relevant for the post-injury response80Role of neuropilins in zebrafish heart regeneration81Highly efficient immunomagnetic purification of cardiomyocytes derived from human pluripotent stem cells82Cardiac progenitor cells posses a molecular circadian clock and display large 24-hour oscillations in proliferation and stress tolerance83Influence of sirolimus and everolimus on bone marrow-derived mesenchymal stem cell biology84Endoglin is important for epicardial behaviour following cardiac injuryCell death and apoptosis - Heart87Ultrastructural alterations reflecting Ca2+ handling and cell-to-cell coupling disorders precede occurrence of severe arrhythmias in intact animal heart88Urocortin-1 promotes cardioprotection through ERK1/2 and EPAC pathways: role in apoptosis and necrosis89Expression p38 MAPK and Cas-3 in myocardium LV of rats with experimental heart failure at melatonin and enalapril introductionTranscriptional control and RNA species - Heart92Accumulation of beta-amyloid 1-40 in HF patients: the role of lncRNA BACE1-AS93Role of miR-182 in zebrafish and mouse models of Holt-Oram syndrome94Mir-27 distinctly regulates muscle-enriched transcription factors and growth factors in cardiac and skeletal muscle cells95AF risk factors impair PITX2 expression leading to Wnt-microRNA-ion channel remodelingCytokines and cellular inflammation - Heart98Post-infarct survival depends on the interplay of monocytes, neutrophils and interferon gamma in a mouse model of myocardial Infarction99Inflammatory cd11b/c cells play a protective role in compensated cardiac hypertrophy by promoting an orai3-related pro-survival signal100Anti-inflammatory effects of endothelin receptor blockade in the atrial tissue of spontaneously hypertensive rats101Mesenchymal stromal cells reduce NLRP3 inflammasome activity in Coxsackievirus B3-induced myocarditis102Mesenchymal stromal cells modulate monocytes trafficking in Coxsackievirus B3-induced myocarditis103The impact of regulatory T lymphocytes on long-term mortality in patients with chronic heart failure104Temporal dynamics of dendritic cells after ST-elevation myocardial infarction relate with improvement of myocardial functionGrowth factors and neurohormones - Heart107Preconditioning of hypertrophied heart: miR-1 and IGF-1 crosstalk108Modulation of catecholamine secretion from human adrenal chromaffin cells by manipulation of G protein-coupled receptor kinase-2 activity109Evaluation of cyclic adenosin-3,5- monophosphate and neurohormones in patients with chronic heart failureNitric oxide and reactive oxygen species - Heart112Hydrogen sulfide donor inhibits oxidative and nitrosative stress, cardiohemodynamics disturbances and restores cNOS coupling in old rats113Role and mechanisms of action of aldehydes produced by monoamine oxidase A in cardiomyocyte death and heart failure114Exercise training has contrasting effects in myocardial infarction and pressure-overload due to different endothelial nitric oxide synthase regulation115S-Nitroso Human Serum Albumin dose-dependently leads to vasodilation and alters reactive hyperaemia in coronary arteries of an isolated mouse heart model116Modulating endothelial nitric oxide synthase with folic acid attenuates doxorubicin-induced cardiomyopathy119Effects of long-term very high intensity exercise on aortic structure and function in an animal model120Electron paramagnetic resonance spectroscopy quantification of nitrosylated hemoglobin (HbNO) as an index of vascular nitric oxide bioavailability in vivo121Deletion of repressor activator protein 1 impairs acetylcholine-induced relaxation due to production of reactive oxygen speciesExtracellular matrix and fibrosis - Heart124MicroRNA-19b is associated with myocardial collagen cross-linking in patients with severe aortic stenosis. Potential usefulness as a circulating biomarker125A new ex vivo model to study cardiac fibrosis126Heterogeneity of fibrosis and fibroblast differentiation in the left ventricle after myocardial infarction127Effect of carbohydrate metabolism degree compensation to the level of galectin-3 changes in hypertensive patients with chronic heart failure and type 2 diabetes mellitus128Statin paradox in association with calcification of bicuspid aortic valve interstitial cells129Cardiac function remains impaired despite reversible cardiac fibrosis after healed experimental viral myocarditisIon channels, ion exchangers and cellular electrophysiology - Heart132Identifying a novel role for PMCA1 (Atp2b1) in heart rhythm instability133Mutations of the caveolin-3 gene as a predisposing factor for cardiac arrhythmias134The human sinoatrial node action potential: time for a computational model135iPSC-derived cardiomyocytes as a model to dissect ion current alterations of genetic atrial fibrillation136Postextrasystolic potentiation in healthy and diseased hearts: effects of the site of origin and coupling interval of the preceding extrasystole137Absence of Nav1.8-based (late) sodium current in rabbit cardiomyocytes and human iPSC-CMs138hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified mutations do not exhibit cellular electrophysiological abnormalitiesMicrocirculation141Atherogenic indices, collagen type IV turnover and the development of microvascular complications- study in diabetics with arterial hypertension142Changes in the microvasculature and blood viscosity in women with rheumatoid arthritis, hypercholesterolemia and hypertensionAtherosclerosis145Shear stress regulates endothelial autophagy: consequences on endothelial senescence and atherogenesis146Obstructive sleep apnea causes aortic remodeling in a chronic murine model147Aortic perivascular adipose tissue displays an aged phenotype in early and late atherosclerosis in ApoE-/- mice148A systematic evaluation of the cellular innate immune response during the process of human atherosclerosis149Inhibition of Coagulation factor Xa increases plaque stability and attenuates the onset and progression of atherosclerotic plaque in apolipoprotein e-deficient mice150Regulatory CD4+ T cells from patients with atherosclerosis display pro-inflammatory skewing and enhanced suppression function151Hypoxia-inducible factor (HIF)-1alpha regulates macrophage energy metabolism by mediating miRNAs152Extracellular S100A4 is a key player of smooth muscle cell phenotypic transition: implications in atherosclerosis153Microparticles of healthy origins improve atherosclerosis-associated endothelial progenitor cell dysfunction via microRNA transfer154Arterial remodeling and metabolism impairment in early atherosclerosis155Role of pannexin1 in atherosclerotic plaque formationCalcium fluxes and excitation-contraction coupling158Amphiphysin II induces tubule formation in cardiac cells159Interleukin 1 beta regulation of connexin 43 in cardiac fibroblasts and the effects of adult cardiac myocyte:fibroblast co-culture on myocyte contraction160T-tubular electrical defects contribute to blunted beta-adrenergic response in heart failure161Beat-to-beat variability of intracellular Ca2+ dynamics of Purkinje cells in the infarct border zone of the mouse heart revealed by rapid-scanning confocal microscopy162The efficacy of late sodium current blockers in hypertrophic cardiomyopathy is dependent on genotype: a study on transgenic mouse models with different mutations163Synthesis of cADPR and NAADP by intracellular CD38 in heart: role in inotropic and arrhythmogenic effects of beta-adrenoceptor signalingContractile apparatus166Towards an engineered heart tissue model of HCM using hiPSC expressing the ACTC E99K mutation167Diastolic mechanical load delays structural and functional deterioration of ultrathin adult heart slices in culture168Structural investigation of the cardiac troponin complex by molecular dynamics169Exercise training restores myocardial and oxidative skeletal muscle function from myocardial infarction heart failure ratsOxygen sensing, ischaemia and reperfusion172A novel antibody specific to full-length stromal derived factor-1 alpha reveals that remote conditioning induces its cleavage by endothelial dipeptidyl peptidase 4173Attenuation of myocardial and vascular arginase activity by vagal nerve stimulation via a mechanism involving alpha-7 nicotinic receptor during cardiac ischemia and reperfusion174Novel nanoparticle-mediated medicine for myocardial ischemia-reperfusion injury simultaneously targeting mitochondrial injury and myocardial inflammation175Acetylcholine plays a key role in myocardial ischaemic preconditioning via recruitment of intrinsic cardiac ganglia176The role of nitric oxide and VEGFR-2 signaling in post ischemic revascularization and muscle recovery in aged hypercholesterolemic mice177Efficacy of ischemic preconditioning to protect the human myocardium: the role of clinical conditions and treatmentsCardiomyopathies and fibrosis180Plakophilin-2 haploinsufficiency leads to impaired canonical Wnt signaling in ARVC patient181Improved technique for customized, easier, safer and more reliable transverse aortic arch banding and debanding in mice as a model of pressure overload hypertrophy182Late sodium current inhibitors for the treatment of inducible obstruction and diastolic dysfunction in hypertrophic cardiomyopathy: a study on human myocardium183Angiotensin II receptor antagonist fimasartan has protective role of left ventricular fibrosis and remodeling in the rat ischemic heart184Role of High-Mobility Group Box 1 (HMGB1) redox state on cardiac fibroblasts activities and heart function after myocardial infarction185Atrial remodeling in hypertrophic cardiomyopathy: insights from mouse models carrying different mutations in cTnT186Electrophysiological abnormalities in ventricular cardiomyocytes from a Maine Coon cat with hypertrophic cardiomyopathy: effects of ranolazine187ZBTB17 is a novel cardiomyopathy candidate gene and regulates autophagy in the heart188Inhibition of SRSF4 in cardiomyocytes induces left ventricular hypertrophy189Molecular characterization of a novel cardiomyopathy related desmin frame shift mutation190Autonomic characterisation of electro-mechanical remodeling in an in-vitro leporine model of heart failure191Modulation of Ca2+-regulatory function by three novel mutations in TNNI3 associated with severe infant restrictive cardiomyopathyAging194The aging impact on cardiac mesenchymal like stromal cells (S+P+)195Reversal of premature aging markers after bariatric surgery196Sex-associated differences in vascular remodeling during aging: role of renin-angiotensin system197Role of the receptor for advanced glycation end-products (RAGE) in age dependent left ventricle dysfunctionsGenetics and epigenetics200hsa-miR-21-5p as a key factor in aortic remodeling during aneurysm formation201Co-inheritance of mutations associated with arrhythmogenic and hypertrophic cardiomyopathy in two Italian families202Lamin a/c hot spot codon 190: form various amino acid substitutions to clinical effects203Treatment with aspirin and atorvastatin attenuate cardiac injury induced by rat chest irradiation: Implication of myocardial miR-1, miR-21, connexin-43 and PKCGenomics, proteomics, metabolomics, lipidomics and glycomics206Differential phosphorylation of desmin at serines 27 and 31 drives the accumulation of preamyloid oligomers in heart failure207Potential role of kinase Akt2 in the reduced recovery of type 2 diabetic hearts subjected to ischemia / reperfusion injury208A proteomics comparison of extracellular matrix remodelling in porcine coronary arteries upon stent implantationMetabolism, diabetes mellitus and obesity211Targeting grk2 as therapeutic strategy for cancer associated to diabetes212Effects of salbutamol on large arterial stiffness in patients with metabolic syndrome213Circulating microRNA-1 and microRNA-133a: potential biomarkers of myocardial steatosis in type 2 diabetes mellitus214Anti-inflammatory nutrigenomic effects of hydroxytyrosol in human adipocytes - protective mechanisms of mediterranean diets in obesity-related inflammation215Alterations in the metal content of different cardiac regions within a rat model of diabetic cardiomyopathyTissue engineering218A novel conductive patch for application in cardiac tissue engineering219Establishment of a simplified and improved workflow from neonatal heart dissociation to cardiomyocyte purification and characterization220Effects of flexible substrate on cardiomyocytes cell culture221Mechanical stretching on cardiac adipose progenitors upregulates sarcomere-related genes

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