A5063156391- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Cardiac Imaging and Diagnostics
- Advanced Glycation End Products research
- Neuroscience and Neural Engineering
- Cardiac Fibrosis and Remodeling
- Tissue Engineering and Regenerative Medicine
- Cardiovascular and exercise physiology
- Electrospun Nanofibers in Biomedical Applications
- Cardiovascular Effects of Exercise
- Neuroscience and Neuropharmacology Research
- Phosphodiesterase function and regulation
- Cardiac pacing and defibrillation studies
- Heart Failure Treatment and Management
- Signaling Pathways in Disease
- Cardiac Ischemia and Reperfusion
- Adipose Tissue and Metabolism
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiac Structural Anomalies and Repair
- Natural Antidiabetic Agents Studies
- Trace Elements in Health
- Cardiovascular Disease and Adiposity
- Estrogen and related hormone effects
Hasselt University
2016-2025
Organ Recovery Systems (Belgium)
2024-2025
Oregon Health & Science University
2021
Biomedical Research Institute
2013-2021
KU Leuven
2006-2016
Institute of Experimental Cardiology
2005-2016
King's College London
2016
Centro Cardiologico Monzino
2016
Imperial College London
2016
University of Florence
2016
During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at junctional complex with T-tubules, containing L-type channels. A partial loss of T-tubules has been described in myocytes failing canine and human hearts. We examined how graded reduction T-tubule density would affect synchrony release.Adult pig ventricular were isolated cultured for 24 72 h. visualized di-8-ANEPPS, [Ca2+]i transients (Fluo-3) recorded during confocal line scan...
In ventricular cardiac myocytes, T-tubule density is an important determinant of the synchrony sarcoplasmic reticulum (SR) Ca2+ release and could be involved in reduced SR ischemic cardiomyopathy. We therefore investigated properties pigs, 6 weeks after inducing severe stenosis circumflex coronary artery (91+/-3%, N=13) with myocardial infarction (8.8+/-2.0% total left mass). Severe dysfunction infarct adjacent myocardium was documented by magnetic resonance Doppler velocity imaging....
Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role left (LV) failure remains incompletely understood. We therefore measured LV PDE5 patients with advanced systolic heart and characterized remodeling after myocardial infarction transgenic mice cardiomyocyte-specific overexpression (PDE5-TG).Immunoblot immunohistochemistry techniques revealed that was greater explanted LVs from...
Rationale : Persistent atrial fibrillation (AF) has been associated with structural and electric remodeling reduced contractile function. Objective To unravel mechanisms underlying sarcoplasmic reticulum (SR) Ca 2+ release in persistent AF. Methods We studied cell shortening, membrane currents, [Ca ] i right myocytes isolated from sheep AF (duration 129±39 days, N=16), compared to matched control animals (N=21). T-tubule density, ryanodine receptor (RyR) distribution, local transients were...
The extent and mechanism of the cardiac benefit early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting abnormalities in Ca 2+ -handling myofilament function. Consequently, we investigated effects 8-weeks voluntary exercise, started after a large MI, on left ventricular (LV) remodeling dysfunction mouse. Exercise had no effect survival, MI size or LV dimensions, improved fractional shortening from 8±1 to 12±1%, LVdP/dt P30 5295±207...
The use of doxorubicin (DOX) chemotherapy is restricted due to dose-dependent cardiotoxicity. Pyridoxamine (PM) a vitamin B6 derivative with favorable effects on diverse cardiovascular diseases, suggesting cardioprotective effect DOX-induced nature PM was investigated in rat model Six-week-old female Sprague Dawley rats were treated intravenously 2 mg/kg DOX or saline (CTRL) weekly for eight weeks. Two other groups received via the drinking water next (DOX+PM) (CTRL+PM). Echocardiography,...
The [Ca 2+ ] i transient of ventricular myocytes during normal excitation-contraction coupling is the summation primary Ca release events, which originate at junction sarcoplasmic reticulum (SR) and T-tubular system. Studies in small mammals have shown a high density sites, but little known larger mammals. We studied spatial distribution SR pig using confocal microscopy. In 69 107 cells, large inhomogeneities were observed along longitudinal scan line. Areas where increase was delayed (time...
Block of Na/Ca exchange (NCX) has potential therapeutic applications, in particular, if a mode-selective block could be achieved, but also carries serious risks for disturbing the normal Ca2+ balance maintained by NCX. We have examined effects partial inhibition NCX SEA-0400 (1 or 0.3 micromol/L) left ventricular myocytes from healthy pigs mice and with heart failure (MLP-/-). During voltage clamp ramps [Ca2+](i) buffering, reverse mode was slightly larger than forward (by 25+/-5%, P<0.05)....
Abstract Exercise training is a low cost and safe approach for reducing the risk of cardiovascular disease development. Currently, moderate-intensity (MIT) most preferred exercise type. However, high-intensity interval (HIIT) gaining interest especially among athletes healthy individuals. In this study, we examined cardiac remodeling resulting from MIT HIIT in rats. Healthy male Sprague-Dawley rats were randomly assigned to or 13 weeks. Animals kept sedentary (SED) used as control. Cardiac...
Endurance exercise training is a promising cardioprotective strategy in type 2 diabetes mellitus (T2DM), but the impact of its intensity not clear. We aimed to investigate whether and how isocaloric moderate-intensity (MIT) high-intensity interval (HIIT) could prevent adverse cardiac remodeling dysfunction that develop T2DM rats. Male rats received Western diet (WD) induce underwent sedentary lifestyle (n = 7), MIT 7) or HIIT 8). Insulin resistance was defined as HOMA-IR value. Cardiac...
Rationale In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases cellular remodeling after myocardial infarction (MI). Objective To characterize RyR functional properties in relation to TT proximity, at baseline and MI. Methods Myocytes were isolated from left ventricle healthy pigs (CTRL) or the area adjacent a Ca2+ transients measured under whole-cell voltage clamp during confocal linescan imaging...
Abstract Aims Melusin is a muscle-specific chaperone protein whose expression required for compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in setting myocardial infarction (MI) using comprehensive multicentre approach. Methods and results Mice overexpressing heart (TG) wild-type controls (WT) were subjected permanent LAD ligation both acute (Day 3) subsequent remodelling (2 weeks) examined. Mortality mice was significant...
Background— L-type calcium channel (LTCC) and Na + /Ca 2+ exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate contractility. Although LTCC inhibition is negative inotropic, NCX has the opposite effect. Combined block may, therefore, offer an advantage for hemodynamics antiarrhythmic efficiency, particularly diseased hearts. In a model of proarrhythmia, dog with chronic atrioventricular block, we investigated whether combined SEA-0400 effective...
Ischemic heart disease is a leading cause of chronic failure. Hibernation (ie, reduction myocardial contractility distal to severe coronary stenosis and reversible on revascularization) an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), acquired >90% (4 6 weeks) resulted in the development hibernating myocardium. Single cardiac myocytes from ISCH area were compared with cells same obtained matched normal (n=12,...
Torsades de pointes (TdP) ventricular tachycardia typically occurs in the setting of early afterdepolarizations; it contributes to arrhythmias and sudden death congenital acquired heart disease. Window L-type Ca2+ current (ICaL) has a central role arrhythmogenesis may be particularly important under beta-adrenergic stimulation. We studied properties ICaL myocytes from dog with chronic atrioventricular block (cAVB) that cardiac hypertrophy an increased susceptibility TdP. Peak densities at...
Rationale: In ventricular myocytes of large mammals with low T-tubule density, a significant number ryanodine receptors (RyRs) are not coupled to the sarcolemma; cardiac remodeling increases noncoupled RyRs. Objective: Our aim was test hypothesis that and RyRs have distinct microdomain-dependent modulation. Methods Results: We studied single from pig left ventricle. The network analyzed in 3-dimension (3D) measure distance membrane release sites. rising phase Ca 2+ transient correlated...