A5027435870- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- 3D Printing in Biomedical Research
- Heart Failure Treatment and Management
- Electrospun Nanofibers in Biomedical Applications
- Apelin-related biomedical research
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Angiogenesis and VEGF in Cancer
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Renin-Angiotensin System Studies
- Nuclear Receptors and Signaling
- Cardiac Fibrosis and Remodeling
- Hormonal Regulation and Hypertension
- Mesenchymal stem cell research
- ICT Impact and Policies
- Immune Response and Inflammation
- Cardiovascular Function and Risk Factors
- Cardiac Ischemia and Reperfusion
- Biomedical Ethics and Regulation
- Cardiac and Coronary Surgery Techniques
- Erythropoietin and Anemia Treatment
- Digital Platforms and Economics
Semmelweis University
2016-2025
Imperial College London
2015-2024
Vodafone (United Kingdom)
2023-2024
Corvinus University of Budapest
2024
AstraZeneca (United Kingdom)
2023
Budapest University of Technology and Economics
2022-2023
Centre for Innovation in Regulatory Science
2022
King's College London
2016
Centro Cardiologico Monzino
2016
Institute of Experimental Cardiology
2016
The orphan receptor APJ and its recently identified endogenous ligand, apelin, exhibit high levels of mRNA expression in the heart. However, functional importance apelin cardiovascular system is not known. In isolated perfused rat hearts, infusion (0.01 to 10 nmol/L) induced a dose-dependent positive inotropic effect (EC 50 : 33.1±1.5 pmol/L). Moreover, preload-induced increase dP/dt max was significantly augmented ( P <0.05) presence apelin. Inhibition phospholipase C (PLC) with U-73122...
Symptoms of cancer cachexia (CC) include fatigue, shortness breath, and impaired exercise capacity, which are also hallmark symptoms heart failure (HF). Herein, we evaluate the effects drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development cardiac wasting, HF, death in rat hepatoma CC model (AH-130). Tumour-bearing rats showed a progressive loss body weight left-ventricular (LV) mass that was associated with deterioration function. Strikingly, bisoprolol...
Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are being developed for tissue repair and as a model system cardiac physiology pathophysiology. However, the signaling requirements of their growth have not yet been fully characterized. We showed that hESC-CM retain capacity increase in size long-term culture. Exposing to hypertrophic stimuli such equiaxial cyclic stretch, angiotensin II, phenylephrine (PE) increased cell volume, percentage with organized sarcomeres, levels ANF,...
Abstract The SERCA-LVAD trial was a phase 2a assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying cardiac isoform sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with left ventricular assist device. one program AAV1/SERCA2a gene therapy trials including CUPID1, CUPID 2 AGENT trials. Enroled subjects were randomised receive single intracoronary infusion × 10 13 DNase-resistant particles or placebo...
Treatment of human disease with embryonic stem cell (hESC)-derived cells is now close to reality, but little known their responses physiological and pathological insult. The ability respond via activation Toll like receptors (TLR) critical in innate immune sensing most tissues, also extends more general danger sensing, e.g. oxidative stress, cardiomyocytes. We used biomarker release gene-array analysis compare hESC before after differentiation, those primary endothelial cells. presence...
Cardiomyocytes from human embryonic stem cells (hESC-CMs) and induced pluripotent (hiPSC-CMs) represent new models for drug discovery.Although hypertrophy is a high-priority target, we found that hiPSC-CMs were systematically unresponsive to hypertrophic signals such as the a-adrenoceptor (aAR) agonist phenylephrine (PE) compared hESC-CMs.We investigated signaling at multiple levels understand underlying mechanism of this differential responsiveness.The expression normal 1 AR gene, ADRA1A,...
Coronary microvascular disease (CMD) and its progression towards major adverse coronary events pose a significant health challenge. Accurate in vitro investigation of CMD requires robust cell model that faithfully represents the cells within cardiac microvasculature. Human pluripotent stem cell-derived endothelial (hPSC-ECs) offer great potential; however, they are traditionally derived via differentiation protocols not readily scalable specified Here, we report development comprehensive...
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) are being investigated as a new source of cardiac cells for drug safety assessment. We developed novel scalable high content microscopy-based method the detection cell death in hPSC-CM that can serve future predictive vitro cardio-toxicological screens. Using rat neonatal ventricular (RVNC) or hPSC-CM, assays nuclear remodelling, mitochondrial status, apoptosis and necrosis were designed using combination fluorescent dyes...
B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and levels normal, despite the persistent increase blood pressure ventricular hypertrophy. this study, role transcriptional mechanisms regulation gene expression were studied angiotensin (Ang) II–induced hypertension by injecting DNA constructs containing promoter (−2200 to 75 bp start site) linked luciferase reporter into rat...
The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart vivo is unknown. Here, we investigated role AT2-R cardiac pressure overload.Rats were infused with vehicle, (Ang II), PD123319 (an antagonist), or combination Ang and via subcutaneously implanted osmotic minipumps for 12 72 hours. II-induced increases mean arterial pressure, left ventricular weight/body weight ratio, elevation skeletal alpha-actin beta-myosin heavy chain mRNA levels not altered by PD123319....
During cardiac hypertrophy, cardiomyocytes (CMs) increase in the size and expression of cytoskeletal proteins while reactivating a foetal gene programme. The process is proposed to be dependent on increased nuclear export and, since pore trafficking has limited capacity, linked decrease import. Our objective was investigate role import control hypertrophy rat human heart failure (HF). In myocardial tissue isolated CMs from patients with dilated cardiomyopathy, increased; Nucleoporin p62,...
This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information references related added subsequently workshop. Comparability is need demonstrate equivalence product after process change; recent publication states that this 'may be difficult for cell-based medicinal products'. Therefore well-managed change required which needs access good science regulatory advice developers are encouraged seek help early. The...
Safety assessment of drug candidates in numerous vitro and experimental animal models is expensive, time consuming intensive. More thorough toxicity profiling already the early discovery projects using human cell models, which more closely resemble physiological types, would help to decrease development costs. In this study we aimed compare different cardiac stem for testing elucidate structure–toxicity relationships novel compounds targeting transcription factor GATA4. By screening effects...
Abstract Aims Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem self‐renewal. Recently, the has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, functional role of this stress‐related death‐related human heart cardiomyocytes not known. In study, we investigated transcriptional co‐activators signalling, YAP TAZ, human‐induced pluripotent cell‐derived (hiPSC‐CMs) response...
Embryonic stem cell-derived cardiomyocytes (ESC-CM) have many of the phenotypic properties authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 200 pregnant women United Kingdom. It is characterized by raised serum bile acids complicated premature delivery unexplained fetal death at late gestation. suggested that caused enhanced arrhythmogenic effect heart, neonatal susceptibility to acid-induced...
Huntington disease (HD; OMIM 143100), a progressive neurodegenerative disorder, is caused by an expanded trinucleotide CAG (polyQ) motif in the HTT gene. Cardiovascular symptoms, often present early stage HD patients, are, general, ascribed to dysautonomia. However, cardio-specific expression of polyQ peptides pathological response murine models, suggesting presence nervous system-independent heart phenotype patients. A positive correlation between repeat size and severity symptoms observed...