A5082354520- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Heart Failure Treatment and Management
- Cardiac electrophysiology and arrhythmias
- Diabetes Treatment and Management
- Cardiovascular Effects of Exercise
- Nitric Oxide and Endothelin Effects
- Atrial Fibrillation Management and Outcomes
- Cardiac Ischemia and Reperfusion
- Cardiovascular Health and Disease Prevention
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- Cardiac, Anesthesia and Surgical Outcomes
- Viral Infections and Immunology Research
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer-related gene regulation
- Muscle Physiology and Disorders
- Heat shock proteins research
- Adipose Tissue and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- COVID-19 Clinical Research Studies
- Cardiovascular Disease and Adiposity
- Vitamin C and Antioxidants Research
- Hippo pathway signaling and YAP/TAZ
Ruhr University Bochum
2015-2025
St. Josef-Hospital
2019-2025
University Hospitals of the Ruhr-University of Bochum
2023-2024
Czech Academy of Sciences, Institute of Physiology
2020-2024
BG University Hospital Bergmannsheil Bochum
2021
Katholisches Klinikum Bochum
2019
Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods results The acute were myocardium from patients HFpEF ZDF obese rats, which treated vivo. As shown immunoblots ELISA, significantly suppressed increased levels ICAM-1, VCAM-1, TNF-α, IL-6 attenuated pathological oxidative...
Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. This study investigates effects molecular mechanisms on human LV. Ventricular myocardium from patients with aortic stenosis preserved LV function sinus rhythm or rate-controlled was studied. showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude...
Abstract Aim We have previously reported that early phase (1 week) of experimental volume overload ( VO ) has an adaptive phenotype while wall stress‐matched pressure PO is maladaptive. Here we investigate the transition from adaptation to heart failure HF in long‐term . Methods and results FVB /N wild‐type mice were subjected induced by aortocaval shunt, followed serial echocardiography until vivo left ventricular ejection fraction was below <50% (135 ± 35 days). Heart evident increased...
The giant protein titin performs structure-preserving functions in the sarcomere and is important for passive stiffness (Fpassive) of cardiomyocytes. Protein kinase D (PKD) enzymes play crucial roles regulating myocardial contraction, hypertrophy, remodeling. PKD phosphorylates myofilament proteins, but it not known whether also a substrate. Here, we aimed to determine thereby modulates cardiomyocyte Fpassive normal failing myocardium. phosphorylation was assessed cardiomyocyte-specific...
Methylation of non-histone proteins is emerging as a central regulatory mechanism in health and disease. The methyltransferase SETD7 has shown to methylate alter the function variety vitro; however, its heart poorly understood. present study investigates role myocardial ischaemic injury.Experiments were performed neonatal rat ventricular myocytes (NRVMs), knockout mice (SETD7-/-) undergoing ischaemia/reperfusion (I/R) injury, left (LV) samples from patients with cardiomyopathy (ICM),...
Our aim was to investigate the effect of nitric oxide (NO)-independent activation soluble guanylyl cyclase (sGC) on cardiomyocyte function in a hypertensive animal model with diastolic dysfunction and biopsies from human heart failure preserved ejection fraction (HFpEF).Dahl salt-sensitive (DSS) rats control were fed high-salt diet for 10 weeks then acutely treated vivo sGC activator BAY 58-2667 (cinaciguat) 30 min. Single skinned passive stiffness (Fpassive) determined myocardium before...
Heart failure is often accompanied by titin-dependent myocardial stiffness. Phosphorylation of titin cGMP-dependent protein kinase I (PKGI) increases cardiomyocyte distensibility. The upstream pathways stimulating PKGI-mediated phosphorylation are unclear. We studied whether C-type natriuretic peptide (CNP), via its guanylyl cyclase-B (GC-B) receptor and cGMP/PKGI signaling, modulates titin-based ventricular compliance. To dissect GC-B–mediated effects endogenous CNP in cardiomyocytes, we...
Hypertrophic cardiomyopathy (HCM) is a complex myocardial disorder with no well-established disease-modifying therapy so far. Our study aimed to investigate how autophagy, oxidative stress, inflammation, stress signalling pathways, and apoptosis are hallmark of HCM their contribution the cardiac dysfunction. Demembranated cardiomyocytes from patients display increased titin-based stiffness (Fpassive), which was corrected upon antioxidant treatment. Titin as main determinant Fpassive...
Abstract Aims Microvascular dysfunction has been proposed to drive heart failure with preserved ejection fraction (HFpEF), but the initiating molecular and cellular events are largely unknown. Our objective was determine when microvascular alterations in HFpEF begin, how they contribute disease progression, pericyte plays a role herein. Methods results dysfunction, characterized by inflammatory activation, loss of junctional barrier function, altered pericyte–endothelial crosstalk, assessed...
Highlights•Sarcomeric dysfunction precedes coronary microvascular in prediabetes.•PKC/rho-kinase activation displaces myosin heads from actin filaments prediabetes.•Oxidative stress and inflammation reduce sGC activity to increase titin stiffness.•Mild hyperglycemia induces cardiomyocyte diastolic ahead of remodeling.AbstractCoronary microvessel endothelial nitric oxide (NO) depletion contribute elevated passive tension cardiomyocytes, predispose the heart failure with preserved ejection...
Key points The Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload. As result missing preload stretch our model, differs from slow force response and has different mechanism. demonstrated two phases. First, sudden increased was momentary equilibrated by LV as higher power strokes strongly‐bound myosin cross‐bridges. Second, slightly delayed recovery SV is...
The prevalence of heart failure with preserved ejection fraction (HFpEF) is continuously rising and predominantly affects older women often hypertensive and/or obese or diabetic. Indeed, there evidence on sex differences in the development HF. Hence, we studied cardiovascular performance dependent age as well pathomechanisms a cellular molecular level.
Oxidative stress is defined as an imbalance between the antioxidant defense system and production of reactive oxygen species (ROS). At low levels, ROS are involved in regulation redox signaling for cell protection. However, upon chronical increase oxidative stress, damage occurs, due to protein, DNA lipid oxidation. Here, we investigated modifications myofilament proteins, their role modulating cardiomyocyte function end-stage human failing hearts. We found altered maximum Ca2+-activated...
BACKGROUND: Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)—a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)—correlates changes in gene expression human failing hearts; however, its role remains poorly understood. This study investigates of cHFpEF. METHODS: Chromatin immunoprecipitation sequencing RNA were used to investigate...
Patients diagnosed with both aortic stenosis (AS) and diabetes mellitus (DM) encounter a distinctive set of challenges due to the interplay between these two conditions. This study aimed investigate effects DM on left ventricle in AS patients, specifically focusing inflammatory response, oxidative stress, their implications for cardiomyocyte function, titin phosphorylation, nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling...
Abstract Background Type 2 diabetes mellitus (T2DM) represents a significant risk factor for cardiovascular disease, particularly heart failure with preserved ejection fraction (HFpEF). HFpEF predominantly affects elderly individuals and women, is characterized by dysfunctions associated metabolic, inflammatory, oxidative stress pathways. Despite being the most prevalent phenotype in patients T2DM, its underlying pathophysiological mechanisms remain inadequately elucidated. Objective This...
The respiratory illness triggered by severe acute syndrome virus-2 (SARS-CoV-2) is often particularly serious or fatal amongst patients with pre-existing heart conditions. Although the mechanisms underlying SARS-CoV-2-related cardiac damage remain elusive, inflammation (i.e. 'cytokine storm') and oxidative stress are likely involved.Here we sought to determine: 1) if cardiomyocytes targeted SARS-CoV-2 2) how promote viral entry into cells. We analysed pro-inflammatory its impact on virus...
The heart is constantly challenged with acute bouts of stretching or overload. Systolic adaptations to these challenges are known but in diastolic stiffness remain unknown. We evaluated myocardial due and characterized the underlying mechanisms.Left ventricles (LVs) intact rat hearts, rabbit papillary muscles strips from cardiac surgery patients were stretched. After stretching, there was a sustained >40% decrease end-diastolic pressure (EDP) passive tension (PT) for 15 min all species...
Protein kinase D (PKD) enzymes play important roles in regulating myocardial contraction, hypertrophy, and remodeling. One of the proteins phosphorylated by PKD is titin, which involved myofilament function. In this study, we aimed to investigate role cardiomyocyte function under conditions oxidative stress. To do this, used mice with a cardiomyocyte-specific knock-out Prkd1, encodes PKD1 (Prkd1loxP/loxP; αMHC-Cre; cKO), as well wild type littermate controls WT). We isolated permeabilized...
Abstract Background Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is highly prevalent and associates a poor outcome. Pathological gene expression in accompanied by changes active histone marks without major alterations DNA methylation. Histone 3 trimethylation at lysine 36 (H3k36me3) - chromatin signature induced the methyltransferase SETD2 strongly correlates human failing hearts; however, its role poorly understood. Here we investigate of cHFpEF. Methods Mice...
Standard heart failure (HF) therapies have failed to improve cardiac function or survival in HF patients with right ventricular (RV) dysfunction suggesting a divergence the molecular mechanisms of RV vs. left (LV) failure. Here we aimed investigate interventricular differences sarcomeric regulation and experimental myocardial infarction (MI)-induced reduced LV ejection fraction (HFrEF). MI was induced by LAD ligation Sprague–Dawley male rats. Sham-operated animals served as controls. Eight...
Abstract Aims Volume overload (VO) induced hypertrophy is one of the hallmarks to development heart diseases. Understanding compensatory mechanisms involved in this process might help preventing disease progression. Methods and results Therefore, present study used 2 months old Wistar rats, which underwent an aortocaval fistula develop VO‐induced hypertrophy. The animals were subdivided into four different groups, two sham operated served as age‐matched controls groups with fistula....
Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular insufficiency syndrome presenting an (EF) of greater than 50% along different proinflammatory and metabolic co-morbidities. Despite previous work provided key insights into our understanding HFpEF, effective treatments are still limited. In the current study we attempted to unravel molecular basis sex-dependent differences in HFpEF pathology. We analyzed left ventricular samples from 1-year-old female male...
Abstract The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, early characteristic of diastolic dysfunction for which no treatment exists. As and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase‐4 (DPP‐4) levels, we investigated whether the clinically approved DPP‐4 inhibitor linagliptin reduces stiffness MetS‐induced cardiac disease. Sixteen‐week‐old obese ZSF1 rats, displaying stiffness, received...