A5005155015- Cardiac Fibrosis and Remodeling
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Aortic aneurysm repair treatments
- Cardiac Ischemia and Reperfusion
- Aortic Disease and Treatment Approaches
- Cardiac Structural Anomalies and Repair
- Infectious Aortic and Vascular Conditions
- Cell Adhesion Molecules Research
- Renin-Angiotensin System Studies
- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Nitric Oxide and Endothelin Effects
- Tissue Engineering and Regenerative Medicine
- PI3K/AKT/mTOR signaling in cancer
- Lipoproteins and Cardiovascular Health
- Blood Coagulation and Thrombosis Mechanisms
- Chemotherapy-induced cardiotoxicity and mitigation
- Hormonal Regulation and Hypertension
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Ion channel regulation and function
University of Alberta
2015-2024
Canadian VIGOUR Centre
2011-2018
University of Toronto
1999-2016
G.V. (Sonny) Montgomery VA Medical Center
2016
University of Mississippi Medical Center
2016
Wm. Jennings Bryan Dorn VA Medical Center
2016
University of South Carolina
2016
University of Virginia
2016
Albert Einstein College of Medicine
2016
Czech Academy of Sciences, Institute of Physiology
2010-2014
Angiotensin converting enzyme 2 (ACE2), a monocarboxylase that degrades angiotensin II to 1-7, is also the functional receptor for severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and highly expressed in lungs heart. Patients with SARS suffered from cardiac disease including arrhythmias, sudden death, systolic diastolic dysfunction.We studied mice infected human strain of SARS-CoV encephalomyocarditis virus examined ACE2 mRNA protein expression. Autopsy heart samples patients...
Abstract Fibroblasts comprise the largest cell population in myocardium. In heart disease, number of fibroblasts is increased either by replication resident myocardial fibroblasts, migration and transformation circulating bone marrow cells, or endothelial/epithelial cells into myofibroblasts. The primary function to produce structural proteins that extracellular matrix (ECM). This can be a constructive process; however, hyperactivity cardiac result excess production deposition ECM...
Pressure overload is accompanied by cardiac myocyte apoptosis, hypertrophy, and inflammatory/fibrogenic responses that lead to ventricular remodeling heart failure. Despite incomplete understanding of how this process regulated, the upregulation tumor necrosis factor (TNF)-alpha after aortic banding in myocardium known. In present study, we tested our hypothesis TNF-alpha regulates inflammatory response, extracellular matrix homeostasis, hypertrophy response mechanical contributes...
Cardiovascular disease is a leading cause of death, and translational research needed to understand better mechanisms whereby the left ventricle responds injury. Mouse models heart have provided valuable insights into that occur during cardiac aging in response variety pathologies. The assessment cardiovascular physiological responses injury or insult an important necessary component this research. With increasing consideration for rigor reproducibility, goal guidelines review provide...
The peptidase action of angiotensin converting enzyme 2 (ACE2) allows it to function as a negative regulator the renin-angiotensin system. Current pharmacotherapies for human heart failure, such ACE inhibitors and aldosterone receptor blockers, increase activity ACE2 in heart. In this study, we investigate mechanism age-dependent cardiomyopathy null mice.Ace2(-/y) mutant mice develop progressive dilated with increased oxidative stress, neutrophilic infiltration, inflammatory cytokine...
Background— Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in cardiac sarcomere determines systolic diastolic function. Loss of titin ischemic hearts has been reported, but mechanism degradation not well understood. Matrix metalloproteinase-2 (MMP-2) localized and, on activation ischemia/reperfusion injury, proteolyzes specific proteins. Here we determine whether an intracellular substrate for MMP-2 if its during contributes...
Background— Despite the mounting clinical burden of heart failure, biomolecules that control myocardial tissue remodeling are poorly understood. TIMP-3 is an endogenous inhibitor matrix metalloproteinases (MMPs) has been found to be deficient in failing human myocardium. We hypothesized expression prevents maladaptive heart, and accordingly, its deficiency mice would alone sufficient trigger progressive cardiac dysfunction similar failure. Methods Results— Mice with a targeted timp-3 were...
Background— Activation of the renin-angiotensin and sympathetic nervous systems may alter cardiac energy substrate preference, thereby contributing to progression heart failure with normal ejection fraction. We assessed qualitative quantitative effects angiotensin II (Ang II) α-adrenergic agonist, phenylephrine (PE), on metabolism in experimental models hypertrophy diastolic dysfunction role Ang type 1 receptor. Methods Results— (1.5 mg·kg −1 ·day ) or PE (40 was administered 9-week-old male...
Rationale : Myocardial infarction (MI) results in remodeling of the myocardium and extracellular matrix (ECM). Tissue inhibitors metalloproteinases (TIMPs) are critical regulators ECM integrity via inhibiting (MMPs). TIMP2 is highly expressed heart only TIMP that, addition to MMPs, required for cell surface activation pro-MMP2. Hence, it difficult predict function as protective (MMP-inhibiting) or harmful (MMP-activating) disease. Objective We examined role cardiac response MI. Methods...
Lung hypoplasia and persistent pulmonary hypertension of the newborn limit survival in congenital diaphragmatic hernia (CDH). Unlike other diseases resulting newborn, infants with CDH are refractory to inhaled nitric oxide (NO). Nitric mediates vasodilatation at birth part via cyclic GMP production. Phosphodiesterase type 5 (PDE5) limits effects NO by inactivation GMP. Because limited success postnatal management CDH, we hypothesized that antenatal PDE5 inhibition would attenuate artery...
Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis a key feature various cardiomyopathies and compromises cardiac systolic diastolic performance. TIMP1 (tissue inhibitor metalloproteinase-1) consistently upregulated in myocardial used as marker fibrosis. However, it remains to be determined whether promotes tissue by inhibiting degradation metalloproteinases or via an metalloproteinase-independent pathway. We examined function using...
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...
AimsTissue inhibitor of metalloproteinases (TIMPs) can mediate myocardial remodelling, hypertrophy, and fibrosis in heart disease. We investigated the impact TIMP2 vs. TIMP3 deficiency angiotensin II (Ang II)-induced remodelling cardiac dysfunction.
Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role HFPEF compared HF reduced (HFREF).This study investigated inflammation mediated by tumor necrosis factor-alpha (TNFα) axis community-based cohorts patients (n = 100), HFREF 100) healthy controls 50). Enzyme-linked immunosorbent assays were used...
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....
Aortic aneurysm, focal dilation of the aorta, results from impaired integrity aortic extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are traditionally known as ECM-degrading enzymes. MMP2 has been associated with aneurysm in patients and animal models. We investigated role thoracic using 2 models remodeling aneurysm.Male 10-week-old MMP2-deficient (MMP2(-/-)) wild-type mice received angiotensin II (Ang II, 1.5 mg/kg/day) or saline (Alzet pump) for 4 weeks. Although both...
Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that each dysregulated in heart failure. Here we show tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator both mouse model left ventricular (LV) dilation dysfunction. Timp-3 −/− mice develop precipitous LV dysfunction reminiscent dilated cardiomyopathy (DCM), culminating early onset failure by 6 weeks, compared with wild-type aortic-banding (AB). deficiency resulted increased TNFα converting enzyme...