A5021934245- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Force Microscopy Techniques and Applications
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- Peptidase Inhibition and Analysis
- Chromosomal and Genetic Variations
- Cardiac electrophysiology and arrhythmias
- Signaling Pathways in Disease
- Tissue Engineering and Regenerative Medicine
- RNA Research and Splicing
- Nuclear Structure and Function
- Protease and Inhibitor Mechanisms
- Adipose Tissue and Metabolism
- Advanced Sensor and Energy Harvesting Materials
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Electrospun Nanofibers in Biomedical Applications
- Cancer-related molecular mechanisms research
- Autophagy in Disease and Therapy
- Congenital heart defects research
- Sirtuins and Resveratrol in Medicine
- Sarcoma Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
Czech Academy of Sciences, Institute of Physiology
2020-2025
University of Münster
2019-2025
Heidelberg University
2012-2024
University Hospital Münster
2022
Martin Luther University Halle-Wittenberg
2012
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
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...
Myocardial passive stiffness is crucial for the heart's pump function and determined by mechanical elements, including extracellular matrix cytoskeletal filaments; however, their individual contributions are controversially discussed difficult to quantify. In this study, we targeted filaments in a mouse model, which enables specific, acute complete cleavage of sarcomeric titin springs. We show vitro that each filament's contribution varies depending on whether elastic or viscous forces...
The giant muscle protein titin is a major contributor to passive force; however, its role in active force generation unresolved. Here, we use novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic quantify how titin-based forces define myocyte ultrastructure mechanics. We show under mechanical strain, as TC doubles from heterozygous homozygous muscles, Z-disks become increasingly out register while are reduced. Interactions with sarcomeric actin filaments...
Despite the high prevalence of heart failure with preserved ejection fraction (HFpEF), pathomechanisms remain elusive and specific therapy is lacking. Disease-causing factors include metabolic risk, notably obesity. However, proteomic changes in HFpEF are poorly understood, hampering therapeutic strategies. We sought to elucidate how syndrome affects cardiac protein expression, phosphorylation acetylation Zucker diabetic fatty/Spontaneously hypertensive F1 (ZSF1) rat model, evaluate...
Argonaute genes are essential for RNA interference, stem cell maintenance and differentiation. The Piwi-like genes, a subclass of the expressed mainly in germline. These may be re-expressed tumors, expression is associated with prognosis several types tumors.We measured mRNAs (Piwi-like 2-4) 125 soft tissue sarcoma (STS) samples by qPCRs. Statistical tests were applied to study correlation levels tumor-specific survival STS patients.In multivariate Cox's regression analyses, we showed that...
Soft tissue sarcoma (STS) is a heterogeneous group of rare malignancies with five-year survival rate approximately 50%. Reliable molecular markers for risk stratification and subsequent therapy management are still needed. Therefore, we analyzed the prognostic potential miR-155-5p miR-203a-3p expression in cohort 79 STS patients. MiR-155-5p was measured from tumor total RNA by qPCR correlated demographic, clinicopathological, data Elevated significantly associated increased stage...
Inherited mutations in contractile and structural genes, which decrease cardiomyocyte tension generation, are principal drivers of dilated cardiomyopathy (DCM)- the leading cause heart failure 1,2 . Progress towards developing precision therapeutics for defining underlying determinants DCM has been centric with negligible attention directed fibroblasts despite their role regulating best predictor severity, cardiac fibrosis 3,4 Given that to reverse is a major limitation both standard care...
Proteasome degradation is an integral part of cellular growth and function. Proteasomal intervention may mitigate adverse myocardial remodeling, but associated with the onset heart failure. Previously, we have demonstrated that increasing abundance cardiac Lmp2 its incorporation into proteasome complexes endogenous mechanism for regulation during hypertrophic remodeling induced by chronic ß-adrenoreceptor stimulation. Here, investigated whether required not driven inflammation show a tipping...
Abstract The giant muscle protein titin is a major contributor to passive force; however, its role in active force generation unresolved. Here, we use novel titin-cleavage (TC) mouse model that allows specific and rapid cutting of elastic quantify how titin-based forces define myocyte ultrastructure mechanics. We show under mechanical strain, as cleavage doubles from heterozygous homozygous TC muscles, Z-disks become increasingly out register while are reduced. Interactions with sarcomeric...
The ubiquitin-proteasome system is a major regulator of protein homeostasis in health and disease by targeted proteolysis. Recent findings show that the heterogeneity proteasome complexes dynamically altered via elevated incorporation non-essential subunits pathogenesis cardiac remodeling. However, impact this regulatory event on remodeling not known. Therefore, aim study was to determine influence subunit Lmp2 induced chronic catecholamine exposure. Wild-type mice subjected 30mg/kg...
Abstract The family of Argonaute genes is essential for stem cell maintenance and RNA interference. Piwi-like as a subclass the are expressed mainly in germline. However, these may be re-expressed tumors, expression associated with prognosis several types tumors. We analyzed mRNAs (Piwi-like 2-4) 125 soft tissue sarcoma (STS) samples by qPCRs. Statistical tests were applied to study correlation levels tumor-specific survival STS patients. In multivariate Cox's regression analyses, we...
The ubiquitin proteasome system regulates cellular function through targeted degradation of signaling and structural proteins. In the mammalian heart, there exist subpopulations with distinct functionality, conferring capacity to adjust proteolytic under physiological pathological conditions. fact, composition seems be highly dynamic during cardiac remodeling. However, whether in turn affects myocardial remodeling is not known. Therefore, aim study was determine specific impact Analyses...
Cardiac remodeling and heart failure are characterized by misaligned adaptations in protein synthesis degradation, harboring the therapeutic potential for interventional harmonization. Partial inhibition of degradation via ubiquitin-proteasome system was reported to reduce acute hypertrophic as well recover systolic function. The studies suggestive an inadequate gain proteasome activity, contributing cardiac failure. Aim identify a common mechanism promoting activity during test whether it...
Introduction: Cardiac remodeling is associated with a dynamic regulation of the ubiquitin-proteasome system. Our previous studies revealed cardiac induction non-essential proteasome subunit low molecular mass peptide 2 (Lmp2) as an early feature beta-adrenoreceptor overstimulation, present in chronic human heart disease. However, impact Lmp2 upregulation on progress has not been characterized detail so far. Objective: Aim study was to monitor contribution mouse model beta-adrenoceptor...
Introduction: The ubiquitin proteasome-system is a main contributor to cellular proteostasis. dynamic regulation of proteasome composition and function during cardiac remodeling has been high interest. To what extend discrete subunits in turn modify remodeling, poorly understood. Objective: Aim the study was investigate contribution non-essential subunit low molecular mass peptide 2 (Lmp2) on function, tissue proteome upon induced hypertrophic remodeling. Methods & Results: We found...