A5032457496- Pulmonary Hypertension Research and Treatments
- Cardiovascular Function and Risk Factors
- Cardiac Fibrosis and Remodeling
- RNA modifications and cancer
- RNA Research and Splicing
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- Cardiovascular Issues in Pregnancy
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neurogenetic and Muscular Disorders Research
- Congenital heart defects research
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Signaling Pathways in Disease
- Adipose Tissue and Metabolism
- Protease and Inhibitor Mechanisms
- NF-κB Signaling Pathways
- Heart Failure Treatment and Management
- Vascular Anomalies and Treatments
- Hormonal Regulation and Hypertension
Justus-Liebig-Universität Gießen
2014-2024
Cardio-Pulmonary Institute
2018-2024
Universities of Giessen and Marburg Lung Center
2014-2024
German Center for Lung Research
2014-2024
Zero to Three
2022
Max Planck Institute for Heart and Lung Research
2009-2014
Max Planck Society
2010
Friedrich-Alexander-Universität Erlangen-Nürnberg
2004-2007
Significance Adhesion G protein-coupled receptors (GPCRs) are expressed in many developing organs, immune cells, and cancer suggesting that they might play an important role physiological pathological functions. Compared with their potential importance, function signaling mechanisms poorly understood. Disruption of the receptor 126 ( Gpr126 ) gene mice leads to lack myelination peripheral nervous system (PNS) heart abnormalities. Similarly, zebrafish mutant line gpr126 st49 exhibits PNS...
Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling the vasculature and right ventricle (RV). Oxidative stress drives process through activation MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, fibrosis.We investigated whether pharmacological inhibition redox-sensitive apical MAPK, ASK1 (apoptosis signal-regulating kinase 1), can halt progression vascular RV remodeling.A selective, orally available inhibitor,...
Proliferation of mammalian cardiomyocytes stops during the first weeks after birth, preventing heart from regenerating injury. Recently, several studies have indicated that induction cardiomyocyte proliferation can be utilized to regenerate heart. Thus, it is important identify novel factors induce cardiomyocytes. Here, we determine effect TNF-related weak inducer apoptosis (TWEAK) on cardiomyocytes, a cytokine known regulate in other cell types. Stimulation neonatal rat with TWEAK resulted...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Objective . The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions right ventricular failure (RVF) remain poorly understood. aim of the current study investigate effects Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B on heart function structure upon artery banding (PAB) mice. Methods Seven days after PAB, mice were treated for 14 with (0.2 mg/kg bid) (5 day). Right remodeling assessed by catheterization, magnetic resonance...
Rationale: Pulmonary arterial hypertension (PAH) is characterized by structural remodeling of pulmonary arteries and arterioles. Underlying biological processes are likely reflected in a perturbation circulating proteins. Objectives: To quantify analyze the plasma proteome patients with PAH using inherited genetic variation to inform on underlying molecular drivers. Methods: An aptamer-based assay was used measure proteins 357 idiopathic or heritable PAH, 103 healthy volunteers, 23 relatives...
Alternative splicing emerges as one of the most important mechanisms to generate transcript diversity. It is regulated by formation protein complexes on pre-mRNA. We demonstrate that phosphatase 1 (PP1) binds factor transformer2-beta1 (tra2-beta1) via a phylogenetically conserved RVDF sequence located RNA recognition motif (RRM) tra2-beta1. PP1 directly tra2-beta1 and dephosphorylates it, which regulates interaction between other proteins. Eight proteins, including SF2/ASF SRp30c, contain an...
Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of histone methyltransferase, Smyd1, founding member SET and MYND domain containing (Smyd) family, interferes with cardiomyocyte maturation proper formation right heart ventricle. The highly related paralogue, Smyd2 is 3 lysine 4- 36-specific methyltransferase expressed brain. Here, we report differentially during development highest expression neonatal heart....
Pulmonary arterial hypertension (PAH) is a fatal disease for which no cure yet available. The leading cause of death in PAH right ventricular (RV) failure. Previously, the TNF receptor superfamily member fibroblast growth factor-inducible molecule 14 (Fn14) has been associated with different fibrotic diseases. However, so far there study demonstrating causal role endogenous Fn14 signaling RV or LV heart disease. purpose this was to determine whether global ablation prevents fibrosis and...
The extracellular matrix is crucial for organogenesis. It a complex and dynamic component that regulates cell behavior by modulating the activity, bioavailability presentation of growth factors to surface receptors. Here, we determined role protein Nephronectin (Npnt) in heart development using zebrafish model system. vertebrate formed as linear tube which myocardium endocardium are separated layer termed cardiac jelly. During development, jelly swells at atrioventricular (AV) canal,...
Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of to pathobiology pulmonary hypertension (PAH) right ventricular (RV) failure not fully understood.The effects Eplerenone (0.1% Inspra® mixed chow) on vascular RV remodeling were evaluated mice (PH) caused by Sugen5416 injection concomitant...
Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Fucoidan, a polysaccharidic ligand the adhesion molecule P-selectin, exhibits antiproliferative properties. The effects fucoidan/P-selectin axis on (PH) after hypoxia remain unexplored.
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and rise in right ventricular (RV) afterload. The increased RV afterload leads to failure (RVF) which reason for high morbidity mortality PAH patients. objective was evaluate therapeutic efficacy antiremodeling potential phosphodiesterase type 5 (PDE5) inhibitor sildenafil soluble guanylate cyclase stimulator riociguat model pressure overload hypertrophy induced artery...
Although the fundamental role of E2F transcription factor family in cell proliferation is well established, specific function E2F4 unclear. On basis findings from culture experiments, generally considered as an inhibitor proliferation. Accumulating evidence suggests, however, that acts activator certain contexts. Here, we have investigated during heart development and proliferating cardiomyocytes. Nuclear expression cardiomyocytes declined mouse development, which correlates with loss...
Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs) mediating a broad range of cellular functions during embryonic development, as well disease and regeneration adulthood. Thus, it is important to understand the underlying molecular mechanisms that modulate this system. Here, we show FGFR-1 can interact with TNF receptor superfamily member fibroblast factor-inducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle reentry. FGF1-induced reentry neonatal...
The adipocytokine adiponectin and its structural homologs, the C1q/TNF-related proteins (CTRPs), increase insulin sensitivity, fatty acid oxidation mitochondrial biogenesis. Adiponectin- CTRP-induced signal transduction has been described to involve receptors a number of co-receptors including Low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is another target proprotein convertase subtilisin/kexin-9 (PCSK9) in addition LDL-receptor (LDL-R). Here, we investigated influence...
Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) in response to chronic hypoxia contributes vascular remodeling hypertension (PH). PH shares numerous similarities with cancer, including a metabolic shift towards glycolysis. In lung adenylate kinase 4 (AK4) promotes reprogramming and metastasis. Against this background, we show that AK4 regulates cell energy metabolism primary human PASMCs. We demonstrate upregulates PASMCs hypoxia-inducible factor-1α...
The ability of the right ventricle to compensate pressure overload determines survival in pulmonary arterial hypertension (PAH). Nitric oxide (NO) reduces ventricular afterload through vasodilation, but excessive NO amounts cause oxidative stress. Oxidative stress drives remodeling arteries and ventricle. In present study, we hypothesized that nitric synthase 2 (NOS2) induction leads contribute impair adaptation PAH. We used a surgical artery banding (PAB) mouse model which dysfunction occur...