A5004855849- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Pulmonary Hypertension Research and Treatments
- Peptidase Inhibition and Analysis
- Sarcoma Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Phosphodiesterase function and regulation
- Congenital heart defects research
- Cancer, Hypoxia, and Metabolism
- Heart Failure Treatment and Management
- Cell Adhesion Molecules Research
- Eicosanoids and Hypertension Pharmacology
- Pregnancy and preeclampsia studies
- Cardiac Structural Anomalies and Repair
- Tissue Engineering and Regenerative Medicine
- Apelin-related biomedical research
- Cardiac Fibrosis and Remodeling
- Cardiovascular Issues in Pregnancy
- Angiogenesis and VEGF in Cancer
- Cardiovascular Disease and Adiposity
- Mitochondrial Function and Pathology
- Cardiac Arrest and Resuscitation
- Virus-based gene therapy research
- Ubiquitin and proteasome pathways
- Renin-Angiotensin System Studies
Medical University of Vienna
2022-2024
Fujirebio (Belgium)
2015-2024
KU Leuven
2014-2024
University of Szeged
2023
Maastricht University
2017
Onze Lieve Vrouwziekenhuis Hospital
2017
Amsterdam University Medical Centers
2017
Universitair Ziekenhuis Leuven
2016
Semmelweis University
2015
Cliniques Universitaires Saint-Luc
2013
Nitric oxide (NO) is an important modulator of cardiac performance and left ventricular (LV) remodeling after myocardial infarction (MI). We tested the effect cardiomyocyte-restricted overexpression one NO synthase isoform, NOS3, on LV MI in mice. structure function before permanent LAD coronary artery ligation were compared transgenic mice with NOS3 (NOS3-TG) their wild-type littermates (WT). Before MI, systemic hemodynamic measurements, echocardiographic assessment fractional shortening...
Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role left (LV) failure remains incompletely understood. We therefore measured LV PDE5 patients with advanced systolic heart and characterized remodeling after myocardial infarction transgenic mice cardiomyocyte-specific overexpression (PDE5-TG).Immunoblot immunohistochemistry techniques revealed that was greater explanted LVs from...
We assessed pulmonary cytochrome P450 (CYP) epoxygenase expression and activity during hypoxia explored the effects of modulating on hypertension. The acute hypoxic vasoconstrictor response was studied in Swiss Webster mice, who express CYP2C29 their lungs. Animals were pretreated with vehicle, inhibitor (N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide) or an soluble epoxide hydrolase. Whereas attenuated constriction (by 52%), hydrolase enhanced 39%), indicating that CYP...
Cardiovascular diseases remain the predominant cause of death worldwide, with prevalence heart failure continuing to increase. Despite increased knowledge metabolic alterations that occur in failure, novel therapies treat observed disturbances are still lacking.Mice were subjected pressure overload by means angiotensin-II infusion or transversal aortic constriction. MicroRNA-146a was either genetically pharmacologically knocked out overexpressed cardiomyocytes. Furthermore, overexpression...
Abstract Circulating endothelial progenitor cells (EPCs) contribute to neovascularization of ischemic tissues and repair injured endothelium. The role bone marrow-derived in hypoxia-induced pulmonary vascular remodeling their tissue-engineering potential hypertension (PH) remain largely unknown. We studied endogenous mobilization homing EPCs green fluorescent protein marrow chimeric mice exposed chronic hypoxia, a common hallmark PH. Despite increased peripheral mobilization, as shown by...
Nitric oxide (NO) activates soluble guanylate cyclase (sGC), a heterodimer composed of alpha- and beta-subunits, to produce cGMP. NO reduces pulmonary vascular remodeling, but the role sGC in responses acute chronic hypoxia remains incompletely elucidated. We therefore studied wild-type (WT) mice with nonfunctional alpha1-subunit (sGCalpha1-/-).sGCalpha1-/- had significantly reduced lung activity vasodilator-stimulated phosphoprotein phosphorylation. Right ventricular systolic pressure did...
Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces injury patients with ST-elevation infarction (STEMI; NCT01398384). randomized a double-blind, placebo-controlled study 250 STEMI to inhale oxygen or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was...
The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its myocardial repair is unknown. Using complementary approaches porcine, murine, and human samples, we show that CLEC4E expression levels the myocardium blood correlate with extent of injury left ventricular (LV) functional impairment. markedly increased vasculature, cardiac myocytes, infiltrating leukocytes ischemic heart. Loss Clec4e signaling associated reduced acute injury,...
Background —Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects NO synthase (NOS) gene transfer on remodeling associated hypoxic hypertension are unknown. Methods and Results —We aerosolized 3×10 9 pfu adenoviral vector containing inducible NOS (AdNOS2), constitutive NOS3 (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled levels, monitored chemiluminescence, were higher AdNOS2-infected rats than AdNOS3-...
Background: Chronic pressure overload predisposes to heart failure, but the pathogenic role of microvascular endothelial cells (MiVEC) remains unknown. We characterized transcriptional, metabolic, and functional adaptation cardiac MiVEC in mice patients with aortic stenosis (AS). Methods: In Tie2-Gfp subjected transverse constriction or sham surgery, we performed RNA sequencing isolated Gfp + -MiVEC validated signature freshly from left ventricle outflow tract right atrium AS. next compared...
Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation neuregulin-1β signaling in heart known contributor failure. The systemically administered recombinant human for 10 days our 5/6 nephrectomy-induced model chronic alleviated progression uremic dysfunction type 4 cardiorenal syndrome. currently presented positive preclinical data...
Background The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. also determined role cardiac myocyte-specific PDE5 adverse LV remodeling mice after transverse aortic constriction (TAC). Methodology/Principal Findings In patients with severe stenosis (AS) undergoing valve...
Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared efficiency vitro vivo derived ICMP age-matched (ACON) healthy young (CON) controls.We isolated 3.6±0.6 BOEC colonies/100×10(6) mononuclear (MNCs) 60-mL blood samples (n=45; age: 66±1 years; LVEF: 31±2%) versus 3.5±0.9 MNCs ACON (n=32; 60±1 years) 2.6±0.4 CON (n=55;...
Enhanced cyclic guanosine monophosphate (cGMP) signaling may attenuate myocardial ischemia-reperfusion injury (I/R) and improve left ventricular (LV) functional recovery after infarction (MI). We investigated the cardioprotection afforded by inhaled NO (iNO), phosphodiesterase 5 (PDE5)-specific inhibitor tadalafil (TAD), or their combination (iNO+TAD) in C57Bl6J mice subjected to 6-minute anterior descending artery ligation followed reperfusion. measured plasma cardiac concentrations of cGMP...
Right ventricular (RV) remodeling comprises multiple adaptation mechanisms to increased pressure- or volume-overload, which in concert determine RV performance as well clinical outcome patients. Here we focus on preclinical models of pressure-overload induced remodeling, better understand a variety inborn acquired cardiopulmonary diseases. Analytical tools include genetic, physiologic, and morphologic techniques animal ranging from zebrafish primates. We compare state-of-the-art non-invasive...
Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management disease, supporting hypothesis inflammation may be driver as well target. However, inflammatory mechanisms during progression cardiac skeletal muscle dysfunction still not characterized. Our objective was characterize inflammasomes myocardial rodent models DMD. Gastrocnemius samples were...
Given the very limited efficacy of doxorubicin (doxo) in soft tissue sarcoma, there is a clear need for more active and less toxic treatments this family diseases. However, due to rarity these malignancies lack reliable preclinical models, development new therapies has lagged behind. We evaluated PhAc-ALGP-doxorubicin (ALGP-doxo), prodrug metabolized doxo by peptidases present tumor cells and/or microenvironment, synovial sarcoma (SynSa) two dedifferentiated liposarcoma (DDLPS)...
Abstract Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal HFpEF-diseased obese ZSF1 rats by echocardiography. First, was confirmed pressure-volume loops compared lean control rats. In echocardiography,...
We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents minimally invasive alternative to existing surgical models. Target cardiac area be photodynamically irradiated was triangulated from the thoracic X-ray scans. acute phase MI histopathologically characterized presence extensive vascular occlusion, hemorrhage, loss transversal...
Abstract The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy a common cardiovascular complication CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins their receptor, KISS1R, exert pivotal influence on pathophysiology modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic...