A5042698152- Blood Coagulation and Thrombosis Mechanisms
- Cardiac Fibrosis and Remodeling
- Renin-Angiotensin System Studies
- Vitamin K Research Studies
- Acute Myocardial Infarction Research
- Cardiovascular and exercise physiology
- Heart Rate Variability and Autonomic Control
- Antiplatelet Therapy and Cardiovascular Diseases
- Mechanical Circulatory Support Devices
- Protease and Inhibitor Mechanisms
- Acute Kidney Injury Research
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Health and Disease Prevention
- Cardiac Ischemia and Reperfusion
- Receptor Mechanisms and Signaling
- Neurological Disease Mechanisms and Treatments
- Cardiovascular Function and Risk Factors
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Coronary Interventions and Diagnostics
- Cardiac Valve Diseases and Treatments
- Barrier Structure and Function Studies
- Heart Failure Treatment and Management
- Lipoproteins and Cardiovascular Health
- Cardiovascular Effects of Exercise
- Hemodynamic Monitoring and Therapy
Maastricht University
2009-2025
Maastricht University Medical Centre
1991-2021
Amsterdam UMC Location University of Amsterdam
2007-2009
Oklahoma Medical Research Foundation
2009
Howard Hughes Medical Institute
2009
University of Groningen
2008
University Medical Center Groningen
2008
Temple University
2007
University of the Free State
2007
Icahn School of Medicine at Mount Sinai
2007
Recent studies have been directed at modulating the heart failure process through inhibition of activated matrix metalloproteinases (MMPs). We hypothesized that a loss MMP inhibitory control by tissue inhibitor (TIMP)-1 deficiency alters course postinfarction chamber remodeling and induced chronic myocardial infarction (MI) in wild-type (WT) TIMP-1 −/− mice. Left ventricular (LV) pressure-volume loops obtained from WT mice demonstrated LV end-diastolic volume [52 ± 4 vs. 71 6 (TIMP-1 ) μl]...
Background Variations in the blood coagulation activity, determined genetically or by medication, may alter atherosclerotic plaque progression, influencing pleiotropic effects of proteases. Published experimental studies have yielded contradictory findings on role hypercoagulability atherogenesis. We therefore sought to address this matter extensively investigating vivo significance genetic alterations and pharmacologic inhibition thrombin formation for onset progression atherosclerosis,...
Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial (MAP) pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation MAP PI was stable from 5 days after surgery. Within each mouse (n = 9), varied by 21+/-6 mm Hg 17+/-4 ms around their respective 24-h averages (97+/-3 89+/-3 ms). Over periods, bimodally distributed clustered two preferential states. Short-term...
We describe the feasibility of chronic measurement cardiac output (CO) in conscious mice. With use gas anesthesia, mice >30 g body wt were instrumented either with transit-time flow probes or electromagnetic placed on ascending aorta. Ascending aortic values recorded 6–16 days after surgery when had fully grown in. In first set experiments, while under ketamine-xylazine estimates stroke volume (SV) obtained by technique compared those simultaneously echocardiography. Transit-time SV...
In spite of major advances in reperfusion therapy for patients presenting with acute coronary syndrome, long-term morbidity is still substantial. A limitation initial treatment myocardial ischemia the lack prevention ischemia/reperfusion (I/R) injury. Activated protein C (APC), a crucial mediator coagulation process, plays prominent role crosstalk between and inflammation provides cytoprotective effects via inhibition apoptosis several human animal studies.APC was administered an model I/R....
Abstract Atherosclerosis is a progressive inflammatory vascular disorder, complicated by plaque rupture and subsequently atherothrombosis. In vitro studies indicate that key clotting proteases, such as factor Xa (FXa), can promote atherosclerosis, presumably mediated through protease activated receptors (PARs). Although experimental showed reduced onset of atherosclerosis upon FXa inhibition, the effect on pre-existing plaques has never been studied. Therefore, we investigated effects...
Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood-brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell-endothelial cell signalling leading to dysfunction as an early mechanism for Bilateral carotid artery stenosis was used mouse model hypoperfusion. Pimonidazole, hypoxic marker, injected prior humane sacrifice at day...
Background The development of vascular cognitive impairment (VCI) and heart failure with preserved ejection fraction (HFpEF) are strongly associated comorbidities such as obesity, diabetes, hypertension, aging. Microvascular dysfunction may be key a pathological step in the during HFpEF. Hence, we aimed to evaluate cerebrovascular phenotype ZSF1 rats identify molecular processes central VCI Methods Male Lean Obese underwent blood pressure glucose measurements, echocardiography series...
In vivo (molecular) imaging of the vessel wall large arteries at subcellular resolution is crucial for unraveling vascular pathophysiology. We previously showed applicability two-photon laser scanning microscopy (TPLSM) in mounted ex vivo. However, TPLSM has thus far suffered from in-frame and between-frame motion artifacts due to arterial movement with cardiac respiratory activity. Now, are suppressed by accelerated image acquisition triggered on performed rat renal mouse carotid arteries,...
Background: SBP and blood pressure variability are independent risk factors for cerebral small vessel disease, a leading cause stroke dementia. Calcium-channel blockers known to reduce may thus offer benefit against Beyond this effect, the impact of calcium-channel on hypertension-induced neuroinflammation, especially, microglial phenotype remains unknown. We aimed study ability amlopidine alleviate microglia inflammation, slow down cognitive dysfunction in aged hypertensive mice. Methods:...
The developmentally important hedgehog (Hh) pathway is activated in ischemic tissue, and exogenously administered Sonic (Shh) supports tissue repair after cardiac ischemia. Hence, it currently assumed that the endogenous increase Shh during ischemia serves a beneficial role limiting damage. To prove or refute this hypothesis, we treated mice with smoothened (Smo) inhibitor cyclopamine to block Hh myocardial reperfusion. experimental induction of resulted activation hallmark features damage,...
Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown vitamin K, thereby potentially aggravating K deficiency. This binding by PBs may offset the beneficial effects of reduction in reducing vascular calcification (VC). Here we assessed whether combining K2 supplementation inhibits VC.We performed 3/4 nephrectomy rats, after warfarin was given for 3 weeks induce Next,...
After myocardial infarction, several neurohumoral systems become activated to maintain systemic perfusion pressure. We evaluated whether this leads alterations of wall structure and contractile reactivity in the thoracic aorta, coronary septal artery, mesenteric resistance arteries. In male Wistar rats, infarction (MI) was induced by permanent ligation left artery. At 5 weeks after MI or sham operation, vessel segments were isolated, chemically sympathectomized, mounted a myograph for...
Abstract Structural changes of the peripheral vascular component as seen during hypertension and atherosclerosis have been suggested heart failure but never reported. Therefore, we studied possible structural alterations in vasculature an experimental model failure, induced by ligation left coronary artery rats. Large conduit resistance-type arteries were excised at 1, 3, 5, 12 weeks after myocardial infarct induction (MI) or sham surgery. Vessel dimensions (medial cross-sectional area...
Abstract The present experiments were designed to test the hypothesis that activation of renin-angiotensin system during compensated heart failure may have adverse effects on cardiac function and change peripheral vascular structure. ANG II (250 ng/kg/min) or saline (0.9% NaCl) infused in myocardial-infarcted sham-operated rats. After 2 weeks, changes investigated. Results: infusion reduced baseline index sham rats but did not further reduce this II-infused MI Total resistance was similarly...
Abstract While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious patients atherosclerotic cardiovascular disease, little is known about effects of this combination treatment on thrombus formation and vascular remodelling upon damage. The aim study was examine and/or injury-induced murine arterial vivo vitro, vessel-wall remodelling, platelet-leukocyte aggregates. Temporary ligation carotid artery C57BL/6 mice, fed a western type diet, led...
Introduction: An inadequate wound healing following myocardial infarction (MI) is one of the main etiologies heart failure (HF) development. Interventions aiming at improving this process may contribute to preserving cardiac function after MI. Our group, as well others, have demonstrated crucial role Wnt/frizzled signaling in post-MI remodeling. In overview, we compared eight different studies which investigated effects administration a peptide fragment Wnt5a, UM206, on infarct mouse MI...
To investigate the effects of long-term treatment with blockers renin-angiotensin system on capillarization and growth fibers in ischemic hind-limb muscles under normal conditions.Ischemia was induced by partial ligation left common iliac artery.Ischemia resulted a significant increase capillary fiber density soleus muscle, decrease mean size muscle cross-sectional area after 4 weeks compared contralateral nonischemic muscle. Ischemia also significantly decreased muscle: body weight ratio We...
Ischemia activates several compensatory mechanisms to restore blood supply. To investigate possible changes in the reactivity of vessels after acute and chronic ischemia skeletal muscle, response (resistance changes) vascular bed angiotensin II (AII) phenylephrine (PE) a hindlimb perfusion model were studied control, acutely ischemic (45 min) chronically (4 weeks) spontaneously hypertensive rats. Furthermore, effects I (AI) involvement local angiotensin-I-converting enzyme (ACE) adaptive...
Abstract Aims Vascular calcification is a hallmark of atherosclerotic burden and can predict the cardiovascular outcome. Vitamin K antagonists (VKA) are widely used anticoagulant drugs to treat patients at risk arterial venous thrombosis but also associated with increase vascular progression. We aim unravel paradox that VKA suppresses plasma coagulation promotes subsequent atherosclerosis-dependent coagulability vessel wall. Methods results Apoe −/− mice were placed on western-type diet...