- Pulmonary Hypertension Research and Treatments
- Cardiovascular Function and Risk Factors
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Vascular Anomalies and Treatments
- Congenital Heart Disease Studies
- Heart Failure Treatment and Management
- Telomeres, Telomerase, and Senescence
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cardiovascular Issues in Pregnancy
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Redox biology and oxidative stress
- Renal and Vascular Pathologies
- Radio Frequency Integrated Circuit Design
- Congenital heart defects research
- Cardiovascular Effects of Exercise
- Inflammasome and immune disorders
- Physiological and biochemical adaptations
- Cardiac Structural Anomalies and Repair
- Cardiac Fibrosis and Remodeling
- Multiple Myeloma Research and Treatments
- Neonatal Respiratory Health Research
- Liver Disease and Transplantation
University of Groningen
2015-2022
University Medical Center Groningen
2015-2022
Adult Congenital Heart Association
2018
Rationale: Pulmonary arterial hypertension (PAH) is a degenerative arteriopathy that leads to right ventricular (RV) failure. BRD4 (bromodomain-containing protein 4), member of the BET (bromodomain and extra-terminal motif) family, has been identified as critical epigenetic driver for cardiovascular diseases.Objectives: To explore therapeutic potential in PAH RVX208, clinically available inhibitor.Methods: Microvascular endothelial cells, smooth muscle cells isolated from distal pulmonary...
The transition from reversible to irreversible pulmonary arterial hypertension involves vascular senescence and can be countered by senolysis.
For indexing cardiac measures in small animal models, tibia length (TL) is a recommended surrogate for body weight (BW) that aims to avoid biases because of disease-induced BW changes. However, we question if by TL mathematically correct. This study aimed investigate the relation between and BW, heart weight, ventricular weights, left diameter optimize current common practice parameters models. In 29 healthy Wistar rats (age 5-34 wk) 116 Black 6 mice 3-17 wk), appeared scale nonlinearly TL1...
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary pressure, inflammation, and neointimal remodeling of arterioles. Serum levels interleukin (IL)-1β IL-18 are elevated in PAH patients may enhance proinflammatory remodeling. NLRP3 inflammasome activation induces cleavage the cytokines IL-1β IL-18, required for their secretion. Pirfenidone (PFD), an antifibrotic anti-inflammatory drug, has been suggested to inhibit activation. We hypothesized that PFD...
Abstract Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by obstructive pulmonary vascular remodelling ultimately leading to right ventricular (RV) failure and death. Disturbed transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling, endothelial cell dysfunction, increased proliferation of smooth muscle cells fibroblasts, inflammation contribute this abnormal remodelling. Peptidyl-prolyl isomerase Pin1 has been identified as critical...
In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The created inserting 18-G needle from the abdominal aorta into adjacent caval vein. Increased has been demonstrated as essential trigger for severe form of distinct phases disease progression, characterized early medial hypertrophy followed neointimal lesions and progressive occlusion small vessels. To measure right heart...
Sex is increasingly emerging as determinant of right ventricular (RV) adaptation to abnormal loading conditions. It unknown, however, whether sex-related differences already occur in childhood. Therefore, this study aimed assess sex a juvenile model early RV pressure load by pulmonary artery banding (PAB) during transition from pre postpuberty. Rat pups (n = 57, 3 wk old, 30-45 g) were subjected PAB or sham surgery. Animals euthanized either before after puberty (4 and 8 postsurgery,...
ObjectivesRight ventricular (RV) failure is a leading cause of death in patients with congenital heart disease. RV kept at bay during childhood. Limited proliferation cardiomyocytes present the postnatal heart. We propose that cardiomyocyte improves adaptation to pressure load (PL). studied response increased PL and role cell cycle activity (CCA) rat pups growing into adulthood.MethodsWe induced day weaning rats (3 weeks; 30-40 g) by pulmonary artery banding followed adulthood (300 g)....
Right ventricular (RV) function and failure are key determinants of morbidity mortality in various cardiovascular diseases. Myocardial fibrosis is regarded as a contributing factor to heart failure, but its importance RV has been challenged. This study aims assess whether myocardial drives the transition from compensated decompensated volume load-induced dysfunction.Wistar rats were subjected aorto-caval shunt (ACS, n = 23) or sham (control, 15) surgery, sacrificed after 1 month, 3 months, 6...
In this protocol, PAH is induced by combining a 60 mg/kg monocrotalin (MCT) injection with increased pulmonary blood flow through an aorto-caval shunt (MCT+Flow). The created inserting 18-G needle from the abdominal aorta into adjacent caval vein. Increased has been demonstrated as essential trigger for severe form of distinct phases disease progression, characterized early medial hypertrophy followed neointimal lesions and progressive occlusion small vessels. To measure right heart...
Abstract Introduction Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterized by abnormal remodelling of pulmonary vessels, leading to increased vascular resistance and right ventricle (RV) failure. This associated with endothelial cell dysfunction, proliferation smooth muscle cells, inflammation, disturbed transforming growth factor beta (TGF-β) signalling. Histone deacetylases (HDACs) have been shown promote inflammation in cells. Although inhibition HDACs using...