A5035524675- Cardiac electrophysiology and arrhythmias
- Connexins and lens biology
- Nicotinic Acetylcholine Receptors Study
- Diet, Metabolism, and Disease
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Liver Disease Diagnosis and Treatment
- Pulmonary Hypertension Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Axon Guidance and Neuronal Signaling
- Metabolism, Diabetes, and Cancer
- Phosphodiesterase function and regulation
- Cardiovascular Effects of Exercise
- Cardiovascular Issues in Pregnancy
- Atrial Fibrillation Management and Outcomes
- Pharmacogenetics and Drug Metabolism
- Hormonal Regulation and Hypertension
- Organic and Inorganic Chemical Reactions
- Sodium Intake and Health
- Cardiac Arrhythmias and Treatments
- Liver Disease and Transplantation
- Receptor Mechanisms and Signaling
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Diet and metabolism studies
Actelion (Switzerland)
2019-2024
Novo Nordisk (Denmark)
2024
University of Copenhagen
2010-2022
Danish National Research Foundation
2011-2016
National Research Foundation
2013
Zealand Pharma (Denmark)
2006-2010
Metabolic syndrome and obesity-related diseases are affecting more people in the Western world. The basis for an effective treatment of these patients is a better understanding underlying pathophysiology. Here, we characterize fructose- fat-fed rats (FFFRs) as new animal model metabolic syndrome. Sprague-Dawley were fed 60 kcal/100 kcal fat diet with 10% fructose drinking water. After 6, 12, 18, 24, 36, 48 wk feeding, blood pressure, glucose tolerance, plasma insulin, glucose, lipid levels...
Increasing evidence points to lipoprotein composition rather than reverse cholesterol transport in the cardioprotective properties of high-density lipoproteins (HDLs). HDL binding receptors at surface cardiomyocytes activates signalling pathways promoting survival, but downstream targets are largely unknown. Here, we investigate by which sphingosine-1-phosphate (S1P) constituent limits cell death induced cardiac ischaemia–reperfusion (I/R). Apolipoprotein M (ApoM) transgenic (Apom-Tg) mice,...
Type 2 diabetes is associated with abnormal electrical conduction and sudden cardiac death, but the pathogenic mechanism remains unknown. This study describes electrophysiological alterations in a diet-induced pre-diabetic rat model examines underlying mechanism. Sprague–Dawley rats were fed either high-fat diet fructose water or normal chow for 6 weeks. The properties of whole heart was analyzed by vivo surface ECG recordings, as wells ex Langendorff perfused hearts during baseline,...
Diabetes increases the risk of cardiovascular complications including arrhythmias, but underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent factor for re-entry present in models with streptozotocin (STZ) induced type 1 diabetes. Whether CV also disturbed 2 diabetes currently unknown.We used Zucker Diabetic Fatty (ZDF) rats, as a model diabetes, and their lean controls Lean (ZDL) rats investigate its response anti-arrhythmic peptide...
Introduction: SK channels have functional importance in the cardiac atrium of many species, including humans. Pharmacological blockage has been reported to be antiarrhythmic animal models atrial fibrillation; however, exact mechanism channel inhibition remains unclear. Objectives: We speculated that together with a direct repolarizing current, previously observed depolarization resting membrane potential (RMP) after reduces sodium availability, thereby prolonging effective refractory period...
Aims Selexipag is a prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension. Cytochrome P450 (CYP) 2C8 involved in metabolism selexipag and its active metabolite, ACT‐333679. This study evaluated interaction clopidogrel, CYP2C8 inhibitor. Methods The had 2‐treatment, 1‐sequence, crossover design. Pharmacokinetics (PK) genotype were assessed healthy male subjects administered (200 μg twice daily [b.i.d.]) alone or with clopidogrel (300 mg single dose 75...
Atrial angiotensin II (Ang II) levels are increased in atrial fibrillation and believed to be important the pathogenesis of arrhythmias. Ang reduces intercellular coupling by inhibiting gap junctions (connexins) may thereby increase risk reentry arrhythmia. The aim current study was investigate acute effect on conduction velocity (CV) tissue from normal chronically infarcted rats.Contractile force measured CV determined time between electrodes placed preparation. Expression AT1a AT1b...
The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to progressive nature disease. An intravenous (IV) formulation was developed provide a option short-term selexipag. In this prospective, multicenter, open-label study, safety, tolerability, and pharmacokinetics temporarily switching between IV were investigated (NCT03187678, ClinicalTrials.gov). PAH patients receiving stable...
Abstract Selexipag is an oral selective prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH) in adults. To date, no targeting pathway pediatric patients. Our goal to identify a dose regimen that results comparable exposures selexipag and its active metabolite JNJ‐68006861 as those shown be efficacious adult PAH Extrapolation from population pharmacokinetic (PK) model developed adults (GRIPHON study; NCT01106014) resulted definition three different...
Insulin resistance impairs the cellular insulin response, and often precedes metabolic disorders, like type 2 diabetes, impacting an increasing number of people globally. Understanding molecular mechanisms in hepatic is essential for early preventive treatments. To elucidate changes signal transduction associated with hepatocellular resistance, we employed a multi-layered mass spectrometry-based proteomics approach focused on receptor (IR) signaling at interactome, phosphoproteome, proteome...
Diabetic patients suffer from both cardiac lipid accumulation and an increased risk of arrhythmias sudden death. This correlation suggests a link between diabetes induced steatosis electrical abnormalities, however, the underlying mechanism remains unknown. We previously showed that conduction velocity slows in Zucker diabetic fatty rats fructose-fat fed rats, models exhibit prominent steatosis. The aim this study was to investigate whether acute reduces per se. Cardiac acutely by perfusing...
Abstract Insulin resistance impairs the cellular insulin response and frequently precedes metabolic disorders, like type 2 diabetes, which are affecting an increasing number of people globally. Given critical role liver in glucose lipid metabolism, understanding molecular mechanisms hepatic is essential for early preventive treatments. To elucidate changes signal transduction associated with hepatocellular resistance, we employed a multi-layered mass spectrometry-based proteomics approach...
Abstract Gap junctions are essential to the function of multicellular animals, which require a high degree coordination between cells. In vertebrates, gap comprise connexins and currently 21 known in humans. The functions highly diverse include exchange metabolites electrical signals cells, as well functions, apparently unrelated intercellular communication. Given diversity junction physiology, regulation activity is complex. structure various some extent; structural rearrangements...
The mechanisms behind development of diet-induced hypertension remain unclear. kidneys play a paramount role in blood volume and pressure regulation. Increases renal vascular resistance lead to increased mean arterial (MAP) due reduced glomerular filtration rate Na+ excretion. Renal may be by several factors, e.g. sympathetic output, activity the renin-angiotensin system or endothelial dysfunction. We examined if 14-week diet rich fat, fructose both led pressure. Sixty male Sprague-Dawley...