A5013826863- Pulmonary Hypertension Research and Treatments
- Tissue Engineering and Regenerative Medicine
- Inflammatory mediators and NSAID effects
- Cardiac Fibrosis and Remodeling
- Cardiovascular Effects of Exercise
- Osteoarthritis Treatment and Mechanisms
- Cardiovascular and exercise physiology
- Pluripotent Stem Cells Research
- Cardiovascular Function and Risk Factors
- Medical Imaging and Pathology Studies
- Cell Adhesion Molecules Research
- Congenital Heart Disease Studies
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Heterotopic Ossification and Related Conditions
- Electrospun Nanofibers in Biomedical Applications
- Bone Metabolism and Diseases
Amsterdam University Medical Centers
2021-2024
Vrije Universiteit Amsterdam
2021-2024
Erasmus MC
2022-2024
Amsterdam Neuroscience
2021
Cardiac fibrosis contributes to the development of heart failure, and is response cardiac fibroblasts (CFs) pressure or volume overload. Limiting factors in CFs research are poor availability human cells tendency transdifferentiate into myofibroblasts when cultured vitro. The possibility generate from induced pluripotent stem (iPSC), providing a nearly unlimited cell source, opens new possibilities. However, behaviour iPSC-CFs under mechanical stimulation has not been studied yet. Our study...
Background: Fibrodysplasia ossificans progressiva (FOP) is caused by an activating mutation (p.R206H) in the type I BMP receptor ALK2, leading to heterotopic ossification (HO) soft connective tissues. While aberrant Activin A-induced SMAD signaling central FOP pathogenesis, global alterations remain poorly understood. Methods: We performed phosphoproteomics, transcriptomics and biochemical analyses mesenchymal cells (MSCs) overexpressing wild-type ALK2-WT or mutant ALK2-R206H receptors...
Pulmonary arterial hypertension (PAH) patients eventually die of right heart failure (RHF). Currently, there is no suitable pre-clinical model to study PAH. Therefore, we aim develop a dysfunction (RHD) using the 3-dimensional engineered tissue (EHT) approach and cardiomyocytes derived from patient-induced pluripotent stem cells (iPSCs) unravel mechanisms that determine fate pressure-overloaded ventricle. iPSCs PAH healthy control subjects were differentiated into (iPSC-CMs), incorporated...
Introduction: A mutation in the Bone Morphogenetic Protein Receptor Type 2 ( BMPR2 ) gene is 70% of hereditary pulmonary arterial hypertension (hPAH) patients causative disease. Previous work demonstrated that right ventricular function more impaired hPAH with a mutation. However, underlying mechanism remains elusive. Moreover, natriuretic peptides, such as N-terminal Brain Natriuretic Peptides (NTproBNP) and Mid Regional proAtrial (MRproANP), are secreted from cardiomyocytes upon stretch...
Introduction: Cardiac fibrosis is the accumulation of extracellular matrix proteins in interstitium and contributes to heart failure. The main source cardiac fibroblasts (cFBs), which are activated as a result pressure overload. Activated fibroblasts, also known myofibroblasts, express α-smooth muscle actin (α-SMA) have an increased production collagen. Here, objective was study behavior induced pluripotent stem cell (iPSC) derived cFBs response pro-fibrotic cytokines mechanical stress....
<b>Introduction:</b> Pulmonary arterial hypertension is a rare, fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. Here, the objective was study cardiac fibrosis as result of mechanical stress. Cardiac fibroblasts (cFBs) were generated using induced pluripotent stem cells (iPSC) and exposed stimulus. <b>Methods:</b> Confluent iPSC differentiated 12 µM CHIR99021 for 24 h RPMI B27 without insulin. Next, recovered h, stimulation 75 ng/ml...
Introduction: Precapillary pulmonary hypertension (PH) is characterized by progressive overload for the right ventricle and heart failure (RHF). N-terminal Brain Natriuretic Peptides (NTproBNP) Atrial (ANP) are secreted from cardiomyocytes upon stretch. NTproBNP used as biomarker RHF. Aim: To study association between ANP pressure in blood, tissue induced pluripotent stem cell derived (iPSC-CMs) PH-patients. Methods: We analyzed 344 PH-patients, 9 controls, PH-patients before 6-months after...
Abstract Low-grade inflammation and pathological endochondral ossification are processes underlying the progression of osteoarthritis, most prevalent joint disease worldwide. In this study, data mining on publicly available transcriptomic datasets revealed EPHA2, a receptor tyrosine kinase associated with cancer, to be both in osteoarthritis. A computational model cellular signaling networks chondrocytes predicted that silico activation EPHA2 healthy increases inflammatory mediators triggers...
Introduction: Pulmonary arterial hypertension (PAH) is a rare fatal disease with vascular remodeling leading to increased right ventricular pressure followed by fibrosis. To study PAH-induced cardiac fibrosis we develop an in vitro model of the failing ventricle, for which fibroblasts (cFBs) were generated from healthy subjects’ and PAH patients’ induced pluripotent stem cells (iPSC). Methods: Confluent iPSC differentiate adding 12 μM CHIR99021 24h RPMI supplemented B27 without insulin....
Introduction: Pulmonary arterial hypertension (PAH) causes right heart failure (HF) and mainly affects females, but males have worse survival. Atrial Natriuretic Peptide (ANP) Brain (BNP), along with N-terminal BNP (NTproBNP), are secreted from cardiomyocytes upon stretch important biomarkers in HF. Sex differences observed NTproBNP levels prognostic value left HF, unknown The aim was to assess sex PAH a translational perspective. Methods: We screened patients baseline measurements...