A5049950602- Pulmonary Hypertension Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- ATP Synthase and ATPases Research
- Cardiomyopathy and Myosin Studies
- Nitric Oxide and Endothelin Effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cardiac pacing and defibrillation studies
- Protease and Inhibitor Mechanisms
- Heat shock proteins research
- Cardiac electrophysiology and arrhythmias
- Blood Coagulation and Thrombosis Mechanisms
- Genetic Neurodegenerative Diseases
- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- Renin-Angiotensin System Studies
- Peptidase Inhibition and Analysis
- Cardiovascular Effects of Exercise
- Apelin-related biomedical research
- Cell Adhesion Molecules Research
Medical Genetics Center
2017-2024
Technical University of Munich
2010-2021
Stanford University
2014-2020
Cardiovascular Institute of the South
2016-2020
Bayer (Germany)
2020
Université Paris Cité
2018
Délégation Paris 7
2018
Institut Jacques Monod
2018
Merck Institute for Science Education
2018
John Wiley & Sons (United States)
2018
Abstract —The heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) is activated under hypoxic conditions, resulting in the upregulation of its target genes plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth (VEGF). PAI-1 VEGF are also induced response to injury, which characterized by activation platelets coagulation cascade as well generation reactive oxygen species (ROS). However, it not known whether HIF-1 stimulated thrombotic factors. We...
NADPH oxidases are important sources of reactive oxygen species (ROS), possibly contributing to various disorders associated with enhanced proliferation. NOX4 appears be involved in vascular signaling and may contribute the response hypoxia. However, exact mechanisms controlling levels under hypoxia not resolved. We found that rapidly mRNA protein pulmonary artery smooth-muscle cells (PASMCs) as well vessels from mice exposed This was dependent on hypoxia-inducible transcription factor...
We previously reported high-throughput RNA sequencing analyses that identified heightened expression of the chromatin architectural factor High Mobility Group AT-hook 1 (HMGA1) in pulmonary arterial endothelial cells (PAECs) from patients who had idiopathic hypertension (PAH) comparison with controls. Because HMGA1 promotes epithelial-to-mesenchymal transition cancer, we hypothesized increased could induce PAECs to a smooth muscle (SM)-like mesenchymal phenotype (endothelial-to-mesenchymal...
Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic inhibitors reverse experimental pulmonary but cause hepatotoxicity in clinical studies. The endogenous inhibitor elafin attenuates hypoxic mice, its potential to improve function BMPR2 severe or vascular pathology the human disease was unknown.To assess elafin-mediated regression of rats lung explants from...
Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins early metastasis. Compelling evidence suggests that elevated levels intracellular oxidative stress contribute to enhanced aggressiveness numerous cancers, possibly including tumors. Using comprehensive microarray analyses RNA interference, we identified six-transmembrane epithelial antigen prostate 1 (STEAP1)-a membrane-bound mesenchymal stem...
Rationale: In pulmonary arterial hypertension (PAH), endothelial dysfunction and obliterative vascular disease are associated with DNA damage impaired signaling of BMPR2 (bone morphogenetic protein type 2 receptor) via two downstream transcription factors, PPARγ (peroxisome proliferator-activated receptor gamma), p53. Objective: We investigated the vasculoprotective regenerative potential a newly identified PPARγ-p53 factor complex in endothelium. Methods Results: this study, we...
Tissue factor (TF) initiates the extrinsic coagulation cascade leading to thrombin formation. Thrombin induces TF mRNA in vascular smooth muscle cells (VSMCs), thereby contributing prolonged procoagulant activity and enhanced thrombogenicity at sites of injury. However, signaling mechanisms mediating this thrombogenic cycle are unclear. Characteristically, injury promotes generation reactive oxygen species (ROS). Because ROS exert functions, we investigated whether NADPH oxidase, an...
The hypoxia-inducible factor-2alpha (HIF-2alpha) contributes to the vascular response hypoxia. Hypoxia inhibits prolyl hydroxylation of N-terminal transactivation domain (N-TAD), thus preventing binding von Hippel-Lindau protein (pVHL) and proteasomal degradation; additionally, hypoxia asparagyl C-TAD, diminishing cofactor recruitment. Reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) have been shown control functions promote remodeling. However, whether HIF-2alpha, ROS, NOXs...
Summary Vascular remodelling isa complex phenomenon associated with restructuring of the vessel wall as a consequence disruption vascular homeostasis. Alterations have been linked to variety cardiovascular disorders including atherosclerosis, injury and pulmonary hypertension. Plasminogen activator inhibitor-1 (PAI-1) is member serpin (serine proteinase inhibitor) family acts an important inhibitor fibrinolysis by interfering plasminogen system. In addition its anti-fibrinolytic effects,...
Cyclic nucleotide phosphodiesterases (PDEs) control the levels of second messengers cAMP and cGMP in many cell types including endothelial cells. Although PDE2 has unique property to be activated by but hydrolyze cAMP, its role function is only poorly understood. Reactive oxygen species (ROS) have been recognized as signaling molecules controlling functions. We thus investigated whether would link ROS generation proliferative responses human umbilical vein cells response thrombin. Thrombin...
Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and indluences angiogenesis, cell survival invasion. Prolyl hydroxylase-3 (PHD3) regulates degradation of HIF-1α. The effects PHD3 in tumour growth are largely unknown.PHD3 expression was analysed human pancreatic cancer tissues lines by real-time quantitative PCR immunohistochemistry. overexpression established stable transfection downregulation short interfering RNA technology. VEGF quantified enzyme-linked immunosorbent assay....
Urotensin-II (U-II) has been considered as one of the most potent vasoactive peptides, although its physiological and pathophysiological role is still not finally resolved. Recent evidence suggests that it promotes angiogenic responses in endothelial cells, underlying signalling mechanisms are unclear. Reactive oxygen species derived from NADPH oxidases major molecules vasculature. Because NOX2 functional we investigated NOX2-containing oxidase U-II-induced angiogenesis elucidated a possible...
Summary Pulmonary vascular remodeling is commonly associated with pulmonary hypertension and characterized by media thickening disordered cellular proliferation, often accompanied fibrin deposition thrombosis in situ. However, the signaling pathways linking these different processes are not well understood. Since GTPase Rac-1 has been suggested to act as a relay various cell types we investigated whether could be link between thrombin signaling,plasminogen activator inhibitor-1 (PAI-1),...
Pulmonary vascular remodeling associated with pulmonary hypertension is characterized by media thickening, disordered proliferation, and in situ thrombosis. The p21-activated kinase-1 (PAK-1) can control growth, migration, prothrombotic activity, the hypoxia-inducible transcription factor HIF-1alpha was remodeling. Here we studied whether PAK-1 are linked expressed of remodeled vessels from patients vasculopathy upregulated, together its upstream regulator Rac1 lung tissue lambs were...
The vasoactive peptide urotensin-II (U-II) has been associated with vascular remodeling in different cardiovascular disorders. Although U-II can induce reactive oxygen species (ROS) by the NADPH oxidase NOX4 and stimulate smooth muscle cell (SMC) proliferation, precise mechanisms linking to processes remain unclear. Forkhead Box O (FoxO) transcription factors have redox signaling control of proliferation apoptosis. We thus hypothesized that FoxOs are involved SMC response toward NOX4. found...
Biallelic mutations in SLC25A46 , encoding a modified solute transporter involved mitochondrial dynamics, have been identified wide range of conditions such as hereditary motor and sensory neuropathy with optic atrophy type VIB ( OMIM : *610826) congenital lethal pontocerebellar hypoplasia PCH ). To date, 18 patients from 13 families reported, presenting the key clinical features atrophy, peripheral neuropathy, cerebellar atrophy. The course disease was highly variable ranging severe...
Deletions in mitochondrial DNA (mtDNA) are an important cause of human disease and their accumulation has been implicated the ageing process. As mtDNA is a high copy number genome, coexistence deleted wild-type molecules within single cell defines heteroplasmy. When molecules, driven by intracellular clonal expansion, reach sufficiently level, biochemical defect emerges, contributing to appearance progression clinical pathology. Consequently, it relevant determine heteroplasmy levels...
Abstract Background The diagnosis of mitochondrial disorders is challenging because the clinical variability and genetic heterogeneity these conditions. Next‐Generation Sequencing (NGS) technology offers a robust high‐throughput platform for nuclear DNA (mtDNA) analyses. Method We developed custom Agilent SureSelect Mito chondrial nd N uclear D isease Panel (Mito‐aND‐Panel) capture kit that allows parallel enrichment subsequent NGS‐based sequence analysis disease‐related genes complete mtDNA...