A5103040583- Pulmonary Hypertension Research and Treatments
- Cardiovascular Function and Risk Factors
- Cardiovascular Effects of Exercise
- Cardiac Fibrosis and Remodeling
- Cardiovascular Issues in Pregnancy
- Cardiac Valve Diseases and Treatments
- Hormonal Regulation and Hypertension
- Cardiac Structural Anomalies and Repair
- Peptidase Inhibition and Analysis
- Liver Disease and Transplantation
- PI3K/AKT/mTOR signaling in cancer
- Vascular Anomalies and Treatments
- Tissue Engineering and Regenerative Medicine
- Renin-Angiotensin System Studies
- Cardiomyopathy and Myosin Studies
- Superconducting Materials and Applications
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiovascular Disease and Adiposity
- Blood Pressure and Hypertension Studies
- Heart Rate Variability and Autonomic Control
- HER2/EGFR in Cancer Research
- ATP Synthase and ATPases Research
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- Medical Imaging and Pathology Studies
Justus-Liebig-Universität Gießen
2019-2023
Cardio-Pulmonary Institute
2018-2023
German Center for Lung Research
2015-2022
Universities of Giessen and Marburg Lung Center
2015-2022
Stanford University
2019-2020
Saarland University
2017
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,...
Background: The ability of the right ventricle (RV) to adapt an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available prevent RV failure, except for heart/lung transplantation. wingless/int-1 (Wnt) signaling pathway plays important role development and may also be implicated adult cardiac remodeling. Methods: Molecular, biochemical, pharmacological approaches were used both vitro vivo...
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...
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by profound vascular remodeling in which pulmonary arteries narrow because of medial thickening and occlusion neointimal lesions, resulting elevated resistance right heart failure. Therapies targeting the neointima would represent significant advance PAH treatment; however, our understanding cellular events driving formation, molecular pathways that control them, remains limited. We comprehensively map stepwise robust,...
In pulmonary arterial hypertension (PAH), progressive structural remodeling accounts for the vasculopathy including obliteration of lung vasculature that causes an increase in vascular resistance and mean blood pressure arteries ultimately leading to right heart failure–mediated death. Deciphering molecular details aberrant signaling cells PAH is fundamental development new therapeutic strategies. We aimed identify kinases as potential drug targets are dysregulated by means a peptide-based...
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...
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...
BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss microvasculature. However, the methods underpinning prior studies did not take into account 3-dimensional (3D) aspects cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to pressure-overloaded RV uncover 3D properties microvascular network and determine whether deficient adaptation contributes failure. METHODS: Heart sections...
Pulmonary arterial hypertension (PAH) is characterized by progressive narrowing of pulmonary arteries, resulting in right heart failure and death. BMPR2 (bone morphogenetic protein receptor type 2) mutations account for most familial PAH forms whereas reduced present many idiopathic forms, suggesting dysfunctional signaling to be a key feature PAH. Modulating therapeutically promising, yet how downregulated unclear.We intended identify pharmaceutically target modifier genes improve PAH.We...
The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model gradual RV from and use it delineate reverse-remodelling events.
Right ventricular (RV) function is the predominant determinant of survival in patients with pulmonary arterial hypertension (PAH). In preclinical models, pharmacological activation BMP (bone morphogenetic protein) signaling FK506 (tacrolimus) improved RV by decreasing afterload. therapy further stabilized three end-stage PAH. Whether has direct effects on pressure-overloaded right ventricle yet unknown. We hypothesized that increasing cardiac improves structure and a model fixed afterload...
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...
New Findings What is the central question of this study? The aim was to investigate whether complementary assessment non‐invasive ultrasound imaging together with closed chest‐derived intracardiac pressure–volume catheterization applicable mice for an in‐depth characterization right ventricular (RV) function even upon maintained pressure overload. main finding and its importance? Characterization RV by use echocardiographic reveals ventricular–arterial decoupling overload, where systolic...
Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking left ventricle (LV), which is responsible for mechanically assisting during contraction. The objective of this study to evaluate biomechanical gene expression changes occurring LV due a mouse model. Nine male mice were divided into two groups: (a) pulmonary arterial banding (PAB, N = 4) (b) sham surgery (Sham, 5). Tagged...
Abstract Therapy-resistant hypertension is a serious medical problem, causing end-organ damage, stroke, and heart failure if untreated. Since the standard of care fails in resistant patients, there still substantial unmet need for effective therapies. Active stimulation soluble guanylyl cyclase via novel stimulators might provide an treatment option. To test this hypothesis, we established new experimental dog model investigated effects cyclase-stimulator BAY 41-2272. In beagle dogs,...
The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact maintained pressure overload RV–pulmonary artery (PA) axis on myocardial strain left (LV) PAH patients comparison a preclinical PA-banding (PAB) mouse model. We hypothesize that PAB model mimics important aspects may be beneficial as surrogate for some longitudinal interventional studies...
<b>Introduction:</b> Apoptosis signal-regulating kinase 1 (ASK1) is a redox-sensitive that acts through activation of p38 and c-Jun N-terminal (JNK) pathways. However, the role ASK1 in pathogenesis right ventricular (RV) remodeling dysfunction unknown. We sought to investigate effects selective inhibitor GS-444217 on pressure overload-induced RV remodeling. <b>Methods:</b> The were evaluated mice subjected pulmonary artery banding (PAB) or sham operation. Seven days after surgery,...
Introduction: Right ventricular (RV) failure is the leading cause of death in patients with pulmonary arterial hypertension (PAH). Capillary rarefaction has been proposed as hallmark RV failure, yet our understanding capillary architecture limited by 2D image analysis. Three-dimensional (3D) confocal deep tissue imaging offers unparalleled opportunity to characterize architectural microvascular changes relationship cardiomyocytes pressure-overloaded failure. Methods and Results: 250 μm heart...
Introduction: Cardiac fibrosis disrupts the myocardial architecture, impairs exchange of oxygen and nutrients, puts heart at risk failure. Snail (SNAI1) is a transcriptional factor involved in cell plasticity that has been linked to fibroblast-to-myofibroblast transition (FMT) hypoxic heart, however, it unknown whether inhibition FMT reduces improves right ventricular (RV) function pressure overloaded RV. We hypothesized necessary for and, as BMP signaling inhibits Snail, two BMPR2...