A5057401954- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- PI3K/AKT/mTOR signaling in cancer
- Iron Metabolism and Disorders
- Cardiomyopathy and Myosin Studies
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiovascular Function and Risk Factors
- Trace Elements in Health
- Hemoglobinopathies and Related Disorders
- Cardiovascular Effects of Exercise
- Cardiac Ischemia and Reperfusion
- Cardiac Fibrosis and Remodeling
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Apelin-related biomedical research
- Metabolism, Diabetes, and Cancer
- Cardiac Arrhythmias and Treatments
- Eicosanoids and Hypertension Pharmacology
- Erythropoietin and Anemia Treatment
- Protease and Inhibitor Mechanisms
- Cardiac Structural Anomalies and Repair
- Heart Failure Treatment and Management
- Nitric Oxide and Endothelin Effects
University of Alberta
2014-2023
Canadian VIGOUR Centre
2017-2023
New York University
2015
Alberta Hospital Edmonton
2013
National Institute of Allergy and Infectious Diseases
2013
Dalhousie University
2000-2011
Coronary artery disease leading to myocardial ischemia is the most common cause of heart failure. Apelin (APLN), endogenous peptide ligand APJ receptor, has emerged as a novel regulator cardiovascular system.Here we show critical role APLN in infarction (MI) and ischemia-reperfusion (IR) injury patients animal models. Myocardial levels were reduced with ischemic Loss increased MI-related mortality, infarct size, inflammation drastic reductions prosurvival pathways resulting greater systolic...
Development of heart failure is known to be associated with changes in energy substrate metabolism. Information on the metabolism that occur limited and results vary depending methods employed. Our aim characterize pressure overload ischaemia–reperfusion (I/R) injury. We used transverse aortic constriction (TAC) mice induce overload-induced failure. Metabolic rates were measured isolated working hearts perfused at physiological afterload (80 mmHg) using 3H- or 14C-labelled substrates. As a...
Iron-overload cardiomyopathy is a prevalent cause of heart failure on world-wide basis and major mortality morbidity in patients with secondary iron-overload genetic hemochromatosis. We investigated the therapeutic effects resveratrol acquired models cardiomyopathy. Murine showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis myocardial fibrosis resulting disease. nuclear acetylated levels FOXO1 corresponding inverse changes SIRT1 corrected by therapy....
Biomechanical stress and cytoskeletal remodeling are key determinants of cellular homeostasis tissue responses to mechanical stimuli injury. Here we document the increased activity gelsolin, an actin filament severing capping protein, in failing human hearts. Deletion gelsolin prevents biomechanical stress-induced adverse heart failure mice. We show that phosphatidylinositol (3,4,5)-triphosphate (PIP3) lipid suppresses actin-severing activities. Accordingly, loss PI3Kα, PIP3-producing enzyme...
The classic phagocyte nicotinamide adenine dinucleotide phosphate oxidase (gp91(phox) or Nox2) is expressed in the heart. Nox2 activation requires membrane translocation of p47(phox) subunit and linked to heart failure. We hypothesized that loss will result decreased reactive oxygen species production resistance failure.To define role pressure overload-induced biomechanical stress.Eight-week-old male null (p47(phox) knockout [KO]), (Nox2KO), wild-type mice were subjected transverse aortic...
Chronic iron overload results in heart and liver diseases is a common cause of morbidity mortality patients with genetic hemochromatosis secondary overload. We investigated the role tissue inhibitor metalloproteinase 3 (TIMP3) overload-mediated injury by subjecting male mice lacking Timp3 ( Timp3-/-) wild-type (WT) to 12 wk chronic Whereas WT developed diastolic dysfunction, iron-overloaded Timp3-/- showed worsened cardiac dysfunction coupled systolic dysfunction. In heart, loss was...
Iron overload cardiomyopathy (IOC) is a major co-morbidity of genetic hemochromatosis and secondary iron with limited therapeutic options. We aim to investigate mechanisms rescue action amlodipine in the murine model overload, characterize changes human cardiac tissue due IOC, compare them animal IOC.As an model, we used male hemojuvelin knockout (HJVKO) mice, which lacked (a co-receptor protein for hepcidin expression). The mice were fed high-iron diet from 4 weeks 1 year age. As rescue,...
Cardiac remodelling in the ischaemic heart determines prognosis patients with disease (IHD), while enhancement of angiogenesis and cell survival has shown great potential for IHD despite translational challenges. Phosphoinositide 3-kinase (PI3K)/Akt signalling pathways play a critical role promoting survival. However, effect PI3Kβ is poorly understood. This study investigates endothelial cardiomyocyte (CM) post-infarct cardiac remodelling.
Myocardial infarction (MI) accounts for a significant proportion of death and morbidity in aged individuals. The risk MI females increases as they enter the peri-menopausal period, generally occurring middle-age. Cytochrome (CYP) 450 metabolizes N-3 N-6 polyunsaturated fatty acids (PUFA) into numerous lipid mediators, oxylipids, which are further metabolised by soluble epoxide hydrolase (sEH), reducing their activity. objective this study was to characterize oxylipid metabolism left...
AimsGenetic mouse models have yielded conflicting conclusions about the role of PI3Kα in heart physiology: specifically, question whether has a direct regulating myocardial contractility. This led to concerns that PI3K inhibitors currently clinical trials for cancer may potentiate cardiotoxicity. Here we seek clarify normal physiology and investigate changes related signalling pathways.
Background Cancer therapies inhibiting PI 3Kα (phosphoinositide 3-kinase-α)-dependent growth factor signaling, including trastuzumab inhibition of HER 2 (Human Epidermal Growth Factor Receptor 2), can cause adverse effects on the heart. Direct is now in clinical trials, but pathway heart atrophy, remodeling, and function context cancer therapy are not well understood. Method Results Pharmacological heart-specific genetic deletion p110α, catalytic subunit 3Kα, was characterized conjunction...
Myocardial fibrosis is a characteristic of various cardiomyopathies, and myocardial fibroblasts play central role in this process. Gelsolin (GSN) an actin severing capping protein that regulates assembly may be involved fibroblast activation. While the GSN mechanical stress-mediated cardiac has been explored, its absence stress not defined. In study, we investigated induced by Angiotensin II (Ang II), profibrotic hormone elevated cardiovascular disease. We utilized mice lacking (Gsn-/- )...
Background Identifying new therapeutic targets for preventing the myocardial ischemia-reperfusion injury would have profound implications in cardiovascular medicine. Myocardial remains a major clinical burden patients with coronary artery disease. Methods and Results We studied several key mechanistic pathways known to mediate cardioprotection 2 independent genetic models reduced cardiac phosphoinositide 3-kinase-α (PI3Kα) activity. P3Kα-deficient (PI3KαDN PI3Kα-Mer-Cre-Mer) showed...