A5060068438- Cardiovascular Function and Risk Factors
- Coronary Interventions and Diagnostics
- Cardiac Imaging and Diagnostics
- Nitric Oxide and Endothelin Effects
- Cardiovascular Disease and Adiposity
- Cardiovascular and exercise physiology
- Cardiac Valve Diseases and Treatments
- Adipose Tissue and Metabolism
- Cerebrovascular and Carotid Artery Diseases
- Pulmonary Hypertension Research and Treatments
- Acute Myocardial Infarction Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Heart Rate Variability and Autonomic Control
- Angiogenesis and VEGF in Cancer
- Cardiac and Coronary Surgery Techniques
- Atherosclerosis and Cardiovascular Diseases
- Animal Nutrition and Physiology
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cardiovascular Effects of Exercise
- Cardiac Ischemia and Reperfusion
- Meat and Animal Product Quality
- Elasticity and Material Modeling
- Cardiovascular Health and Disease Prevention
- Pharmacological Effects and Assays
- Congenital heart defects research
Erasmus MC
2016-2025
Erasmus University Rotterdam
2012-2025
Netherlands Heart Institute
2011-2017
Universidad de Granada
2016
Amsterdam UMC Location University of Amsterdam
2002-2008
University of Minnesota Medical Center
2008
University of Amsterdam
2002-2006
Aarhus University
2004
More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance dysfunction is higher in females and associates multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these induce systemic inflammation, coronary microvascular dysfunction, oxidative stress, leading to myocardial...
Remodeling of small arteries is essential in the long-term regulation blood pressure and flow to specific organs or tissues. A large part change vessel diameter may occur through non-growth-related reorganization wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes inward remodeling arteries. vivo rat mesenteric arteries, induced by low flow, attenuated inhibition tTG. Rat skeletal muscle expressed tTG, as identified Western...
Distal to a chronic coronary artery stenosis, structural remodeling of the microvasculature occurs. The microvascular functional changes distal stenosis have not been studied in detail. We tested hypothesis that is accompanied by altered regulation vasomotor tone with increased responsiveness endothelin-1. Vasomotor was microvessels from healthy control swine and 3 4 months after implantation an occluder causes progressive narrowing, resulting regional left ventricular dysfunction blunted...
Abstract Objectives : To study the effect of endothelial progenitor cell (EPC) capture on vascular response to coronary stenting. Background The introduction drug‐eluting stents has reduced need for target lesion revascularization, but their delayed healing, inflammation, and dysfunction emphasized design strategies that improve current DES. One such strategy is endothelialization by capturing CD34‐positive cells stent surface. first human clinical trial using EPC showed safety neointimal...
Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo DM high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation attenuated endothelin (ET)-1-mediated vasoconstriction. Here studied the progression CMD after 15 same animal model CAD. Ten male were fed a HFD absence (HFD, n = 5) or presence streptozotocin-induced (DM...
Abstract Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial ‘Ischemia No Obstructive Coronary Artery disease’ (INOCA). In the present study, we tested hypothesis results in perturbations perfusion oxygen delivery using a novel swine model multiple comorbidities. DM (streptozotocin),...
Detailed evaluation of coronary function early in diabetes mellitus (DM)-associated artery disease (CAD) development is difficult patients. Therefore, we investigated conduit and small a preatherosclerotic DM porcine model with type 2 characteristics. Streptozotocin-induced pigs on saturated fat/cholesterol (SFC) diet (SFC + DM) were compared control SFC standard (control) diets. showed DM-associated metabolic alterations atherosclerosis the aorta. Endothelium-dependent vasodilation to...
Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has proposed as a critical factor contributing to the reduced adaptability of pigs stress. Here we tested hypothesis that cardiac dimensions and pump function heavy are disproportionally low for their body weight, investigated potential underlying mechanisms. The results from present study indeed demonstrate values stroke volume output with bodyweights over 150 kg. Importantly, these were not...
Withdrawal of the endothelin (ET)-mediated vasoconstrictor influence contributes to metabolic coronary vasodilation during exercise. Because production nitric oxide (NO) and prostanoids increases with increasing shear stress because NO are able modify release ET, we hypothesized that withdrawal ET-mediated vasoconstriction exercise is mediated through and/or prostanoids. To test this hypothesis, 19 chronically instrumented swine were studied at rest while running on a treadmill up 85-90%...
T-type calcium channels may be involved in the maintenance of myogenic tone. We tested their role isolated rat cremaster arterioles obtained after CO 2 anesthesia and decapitation. Total RNA was analyzed by RT-PCR Southern blotting for channel expression. observed expression voltage-operated (Ca V ) Ca 3.1 (T-type), 3.2 1.2 (L-type) ( n= 3 rats). Amplification products were only presence reverse transcriptase cDNA. Concentration-response curves relatively specific L-type blocker verapamil...
Coronary blood vessels are compressed by the contracting myocardium. This leads to oscillations in flow especially subendocardium. We examined effects of steady and oscillating on isolated, cannulated subendocardial subepicardial porcine arterioles. Steady flow-induced dilation both vessel types, up 12.9+/-0.8% passive diameter subendocardials 9.6+/-1.4% subepicardials at 40 dyne/cm2. Dilation was completely abolished after treatment with 10 micromol/L L-NNA. Sinusoidal modulation 1.5 Hz 50%...
Abstract It is well known that high von Willebrand factor (VWF) and VIII (FVIII) levels are associated with an increased risk of cardiovascular disease. still debated whether VWF FVIII biomarkers endothelial dysfunction atherosclerosis or they have a direct causative role. Therefore, we aimed to unravel the pathophysiological pathways factors. First, performed randomized controlled trial in 34 Göttingen miniswine. Diabetes mellitus (DM) was induced streptozotocin hypercholesterolemia (HC)...
Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress produced endothelial dysfunction, altering control tone via loss NO bioavailability, which was associated with an increase circulating endothelin (ET). In the present study, we tested hypotheses (1) ROS scavenging (2) ET
The capacity for myocardial perfusion depends on the structure of coronary microvascular bed. Coronary microvessels may adapt their to various stimuli. We tested whether local pressure profile affects tone and remodeling porcine microvessels. Subendocardial vessels (approximately 160 microm, n=53) were cannulated kept in organoid culture 3 days under different transvascular profiles: Osc 80: mean 80 mmHg, 60 mmHg peak-peak sine wave pulsation amplitude at 1.5 Hz; St steady mmHg; 40: 40 30...
Coronary blood flow is controlled via several vasoactive mediators that exert their effect on coronary resistance vessel tone through activation of K(+) channels in vascular smooth muscle. Because Ca(2+)-activated (K(Ca)(+)) are the predominant vasculature, we hypothesized K(Ca)(+) channel contributes to exercise-induced vasodilation. In view previous observations ATP-sensitive (K(ATP)(+)) contribute, particular, resting tone, additionally investigated integrated control by and K(ATP)(+)...
BackgroundWe studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine a high fat diet without (HFD) or with diabetes (DM + HFD).MethodsFive DM HFD and five underwent BVS top plaques, were six months later. Conduit artery segments >5 mm proximal to corresponding non-scaffolded arteries, small arteries within flow-territory scaffolded harvested for vitro vasoreactivity studies.ResultsConduit edges showed reduced...
Background Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings DN, which represent one manifestation ongoing systemic damage. Recently, sidestream dark-field (SDF) imaging has emerged as noninvasive tool that enables to visualize microcirculation. In this study, we investigated whether changes microvasculature induced by DM and an atherogenic diet...
Abstract The prevalence of diabetic metabolic derangement (DMetD) has increased dramatically over the last decades. Although there is increasing evidence that DMetD associated with cardiac dysfunction, early DMetD-induced myocardial alterations remain incompletely understood. Here, we studied DMetD-related changes in a clinically relevant large animal model. was established adult male Göttingen miniswine by streptozotocin injections and high-fat, high-sugar diet, while control animals...