A5054895539- Cardiomyopathy and Myosin Studies
- Cardiovascular Effects of Exercise
- Mechanical Circulatory Support Devices
- Cardiac Structural Anomalies and Repair
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Fuel Cells and Related Materials
- Skin and Cellular Biology Research
- Viral Infections and Immunology Research
- Tissue Engineering and Regenerative Medicine
- RNA Research and Splicing
- Muscle Physiology and Disorders
- Transplantation: Methods and Outcomes
- Ion channel regulation and function
- Sports injuries and prevention
- Nuclear Structure and Function
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- Cardiac Arrest and Resuscitation
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Cardiac Arrhythmias and Treatments
- RNA and protein synthesis mechanisms
Heart and Diabetes Center North Rhine-Westphalia
2016-2025
Ruhr University Bochum
2016-2025
LWL-Universitätsklinikum Bochum
2008-2023
University Hospitals of the Ruhr-University of Bochum
2009-2023
Klinik Bad Oexen
2001-2021
Imperial College London
2012-2017
Medizinische Hochschule Hannover
2017
Universitätsmedizin Göttingen
2017
University Hospital of Bern
2015
Columbia University Irving Medical Center
2012
Background— Heart failure is associated with impaired myocardial metabolism a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart and mechanical unloading the failing myocardium corrects metabolism. Methods Results— analyzed serum 61 patients (body mass index, 26.5±5.1 kg/m 2 ; age, 51±12 years) obtained during left ventricular assist device implantation at explantation...
Abstract Aims Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk mortality. It unclear whether direct cardiomyocytes or mainly secondary lung inflammation. Here, we investigate are permissive for infection. Methods results Two strains infected human induced pluripotent stem cell-derived demonstrated detection...
RBPs (RNA-binding proteins) have been described to be expressed and regulated in various organs including the heart. Little is known about role of heart failure induced by chemotherapy drug doxorubicin their interaction with circular RNAs.We aimed identify key involved doxorubicin-mediated elucidate function.Global transcriptome profiling from murine myocardium exposed identified 5 differentially RBPs. Expression RBP QKI (Quaking) response was strongly downregulated rodent cardiomyocytes...
Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized transcriptome 880,000 nuclei from 18 control 61 failing, nonischemic human hearts with pathogenic DCM ACM or idiopathic disease. We performed genotype-stratified analyses ventricular cell lineages transcriptional states. The resultant atlas demonstrated distinct...
Background— Alterations in the balance of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) are involved left ventricular (LV) remodeling. Whether expression is related to interstitial fibrosis or LV dysfunction patients with chronic pressure overload–induced hypertrophy, however, unknown. Methods Results— Therefore, cardiac biopsies were taken 36 isolated aortic stenosis (AS) 29 control without hypertrophy. Microarray analysis revealed significantly increased...
Induced pluripotent stem (iPS) cells generated from accessible adult of patients with genetic diseases open unprecedented opportunities for exploring the pathophysiology human in vitro. Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is an inherited cardiac disorder that caused by mutations ryanodine receptor 2 gene (RYR2) and characterized stress-induced arrhythmia can lead to sudden death young individuals. The aim this study was generate iPS a patient CPVT1 determine...
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease, frequently accompanied by sudden cardiac death and terminal failure. Genotyping of ARVC patients might be used for palliative treatment the affected family. We genotyped a cohort 22 referred to molecular genetic screening in our center mutations desmosomal candidate genes JUP, DSG2, DSC2, DSP PKP2 known associated with ARVC. In 43% cohort, we found disease-associated sequence variants. addition,...
Background— Inhibition of tyrosine kinases, including platelet-derived growth factor receptor, can reduce pulmonary arterial pressure in experimental and clinical hypertension. We hypothesized that inhibition the serine/threonine kinases Raf-1 (also termed c-Raf) b-Raf addition to effectively controls vascular right heart remodeling Methods Results— investigated effects novel multikinase inhibitor sorafenib, which inhibits as well comparison imatinib, a kinase inhibitor, on hemodynamics,...
In vitro models incorporating the complexity and function of adult human tissues are highly desired for translational research. Whilst vital slices myocardium approach these demands, their rapid degeneration in tissue culture precludes long-term experimentation. Here, we report preservation structure performance under conditions physiological preload, compliance, continuous excitation. biomimetic culture, prepared from explanted failing hearts attain a stable state contractility that can be...
Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement different physiological pathophysiological processes. However, functional role ORs heart is still unclear. Here, we firstly report characterization an OR heart. Initial next-generation sequencing analysis revealed pattern adult fetal identified fatty acid-sensing OR51E1 as most highly expressed both cardiac development stages. An extensive ligand profile by luciferase...
Heterozygous truncating variants in TTN (TTNtv), the gene coding for titin, cause dilated cardiomyopathy (DCM), but underlying pathomechanisms are unclear and disease management remains uncertain. Truncated titin proteins have not yet been considered as a contributor to development. Here, we studied myocardial tissues from nonfailing donor hearts 113 patients with end-stage DCM expression identified TTNtv 22 (19.5%). We directly demonstrate haploinsufficiency TTNtv-DCM absence of...
Desmin (DES) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently, DES were described in patients inherited arrhythmogenic right ventricular cardiomyopathy/dysplasia, although their cellular molecular pathomechanisms are not precisely known. Our aim is to describe clinically functionally the novel DES-p.Glu401Asp mutation as a of left cardiomyopathy/dysplasia.We identified p.Glu401Asp large Spanish family cardiomyopathy/dysplasia high incidence...
Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel option. However, the regulation SK-channels human cardiomyocytes and its modification patients with AF are poorly understood were object this study. Apamin-sensitive SK-channel current (ISK) action potentials recorded right-atrial from sinus rhythm control (Ctl) or (long-standing persistent) chronic (cAF). ISK was significantly...
Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) a critical determinant quality control (PQC) CM. CM-specific loss mUsp5 leads to the polyubiquitin chains aggregates, remodeling, eventually DCM. USP5 interacts with key components machinery,...
In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile calcium homeostasis, ventricular assist device (VAD) is implanted for bridging cardiac transplantation results in myocardial unloading. Although phenotype changes the failing are assumed result from hemodynamic overload, reversibility of these under unloading unknown.By use quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were...
Background— Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated impaired adipokine signaling hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation correct in HF. Methods Results— Circulating insulin, adiponectin, leptin, resistin levels were measured 36 before after VAD 10 healthy...
Long QT syndromes (LQTS) are heritable diseases characterized by prolongation of the interval on an electrocardiogram, which often leads to syncope and sudden cardiac death. Here we report generation induced pluripotent stems (iPS) cells from two patients with LQTS type 3 carrying a different point mutation in sodium channel Nav1.5 (p.V240M p.R535Q) functional characterization cardiomyocytes (CM) derived them. The iPS exhibited all characteristic properties stem cells, maintained...
Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM not completely known. We identified next-generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in small family with combination skeletal myopathy an early onset disease. encodes αB-crystallin, member heat shock protein family, which highly expressed cardiac muscle. In addition to silico prediction analysis, our...