A5018267752- Eicosanoids and Hypertension Pharmacology
- Cardiac Ischemia and Reperfusion
- Cardiovascular Function and Risk Factors
- Hormonal Regulation and Hypertension
- Nitric Oxide and Endothelin Effects
- Fatty Acid Research and Health
- Pharmacogenetics and Drug Metabolism
- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Alcohol Consumption and Health Effects
- Inflammatory mediators and NSAID effects
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Heart Failure Treatment and Management
- Cardiac Imaging and Diagnostics
- Cholinesterase and Neurodegenerative Diseases
- Signaling Pathways in Disease
- Inflammasome and immune disorders
- Environmental Toxicology and Ecotoxicology
- Cardiac electrophysiology and arrhythmias
- Aquaculture Nutrition and Growth
- Peptidase Inhibition and Analysis
- Cardiac Fibrosis and Remodeling
- Glutathione Transferases and Polymorphisms
University of Alberta
2016-2025
Canadian VIGOUR Centre
2016-2022
Pharmaceutical Biotechnology (Czechia)
2011-2020
Alberta Hospital Edmonton
2012-2019
The University of Texas MD Anderson Cancer Center
2013
Trinity College Dublin
2013
St. John's School
2012
In-Q-Tel
2009
National Institutes of Health
2005-2006
Duke Medical Center
2004-2006
Background: Although empagliflozin was shown to profoundly reduce cardiovascular events in diabetic patients and blunt the decline cardiac function nondiabetic mice with established heart failure (HF), mechanism of action remains unknown. Methods Results: We treated 2 rodent models HF 10 mg/kg per day measured activation NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome heart. show for first time that beneficial effects reduced ejection fraction (HF [HFrEF]; n=30–34)...
SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because induction of late component cardiac sodium channel current (late-
Human CYP2J2 is abundant in heart and active the biosynthesis of epoxyeicosatrienoic acids (EETs); however, functional role this P450 its eicosanoid products remains unknown. Transgenic mice with cardiomyocyte-specific overexpression were generated. transgenic (Tr) have normal anatomy basal contractile function. Tr hearts improved recovery left ventricular developed pressure (LVDP) compared wild-type (WT) after 20 minutes ischemia 40 reperfusion. Perfusion selective epoxygenase inhibitor N...
Cytochrome P450 epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which are converted dihydroxyeicosatrienoic (DHETs) by soluble epoxide hydrolase ( Ephx2 , sEH). To examine the functional role of sEH in heart, mice with targeted disruption gene were studied. Hearts from null have undetectable levels mRNA and protein cannot convert EETs DHETs. normal heart anatomy basal contractile function, but higher fatty epoxide:diol ratios plasma cardiomyocyte cell culture...
Endothelial dysfunction contributes to the development of coronary heart disease (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in vasculature and regulates endothelial function. We sought determine whether genetic variation soluble ( EPHX2 ) was associated with risk CHD. genotyped 2065 Atherosclerosis Risk Communities study participants (1085 incident CHD cases, 980 non-cases) for 10 previously identified polymorphisms . Using a case–cohort design, associations...
Background: Previous studies have shown beneficial effects of acute infusion the primary ketone body, β-hydroxybutyrate, in heart failure (HF). However, whether chronic elevations circulating ketones are remains unknown. Methods: To chronically elevate mice, we deleted expression ketolytic, rate-limiting-enzyme, SCOT (succinyl-CoA:3-ketoacid-CoA transferase 1; encoded by Oxct1 ), skeletal muscle. Tamoxifen-inducible muscle-specific Muscle− / − knockout (n=32) mice and littermate controls...
Endothelial cells play a vital role in the maintenance of cardiovascular homeostasis. Epoxyeicosatrienoic acids (EETs), cytochrome P-450 (CYP) epoxygenase metabolites arachidonic acid endothelial cells, possess potent and diverse biological effects within vasculature. We evaluated overexpression CYP epoxygenases on tumor necrosis factor-α (TNF-α)-induced apoptosis bovine aortic cells. significantly increased cell viability inhibited TNF-α induction as by morphological analysis nuclear...
Human cytochrome P-450 (CYP)2J2 is abundant in heart and active biosynthesis of epoxyeicosatrienoic acids (EETs). Recently, we demonstrated that these eicosanoid products protect myocardium from ischemia-reperfusion injury. The present study utilized transgenic (Tr) mice with cardiomyocyte-specific overexpression human CYP2J2 to investigate protection toward toxicity resulting acute (0, 5, or 15 mg/kg daily for 3 days, followed by 24-h recovery) chronic 1.5, 3.0 biweekly 5 wk, 2-wk...
We investigated whether treatment of mice with established pressure overload-induced heart failure (HF) the naturally occurring polyphenol resveratrol could improve functional symptoms clinical HF such as fatigue and exercise intolerance. C57Bl/6N were subjected to either sham or transverse aortic constriction surgery induce HF. Three weeks postsurgery, a cohort (%ejection fraction <45) was administered (~450 mg·kg −1 ·day ) vehicle for 2 wk. Although percent ejection similar between both...
Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and the applicability of monitoring it non‐invasively human explanted hearts. Methods Results Biventricular tissue levels were measured both failing (n=138) non‐failing control (NFC, n=46) Clinical phenotyping was complemented with comprehensive assessment myocardial remodeling mitochondrial functional profiles,...
Abstract Influenza is a significant cause of morbidity and mortality worldwide despite extensive research vaccine availability. The cyclooxygenase (COX) pathway important in modulating immune responses also major target nonsteroidal anti-inflammatory drugs (NSAIDs) the newer COX-2 inhibitors. purpose present study was to examine effect deficiency COX-1 or on host response influenza. We used an influenza A viral infection model wild type (WT), COX-1−/−, COX-2−/− mice. Infection induced less...
Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase metabolites of arachidonic acid involved in regulating pathways promoting cellular protection. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing death. Considering it is unknown how regulate cell death processes, the major focus current study was to investigate their role autophagic HL-1 cells neonatal cardiomyocytes (NCMs) during starvation. employed dual-acting...
Glucose oxidation is a major contributor to myocardial energy production and its contribution orchestrated by insulin. While insulin can increase glucose indirectly enhancing uptake glycolysis, it also directly stimulates mitochondrial oxidation, independent of increasing or through activating pyruvate dehydrogenase (PDH), the rate-limiting enzyme oxidation. However, how PDH not known. To determine this, we characterized impacts modifying signaling kinases, namely protein kinase B (Akt),...