A5034848408- Nitric Oxide and Endothelin Effects
- Cardiac Fibrosis and Remodeling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Diabetes Treatment and Management
- Cardiovascular Function and Risk Factors
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiac Ischemia and Reperfusion
- Angiogenesis and VEGF in Cancer
- Adipose Tissue and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Neuropeptides and Animal Physiology
- Heart Failure Treatment and Management
- Regulation of Appetite and Obesity
- Pluripotent Stem Cells Research
- Hormonal Regulation and Hypertension
- Pharmacology and Obesity Treatment
- Retinal Diseases and Treatments
- Peptidase Inhibition and Analysis
- Tissue Engineering and Regenerative Medicine
- Redox biology and oxidative stress
- Cardiovascular Disease and Adiposity
- Cardiac, Anesthesia and Surgical Outcomes
- Peroxisome Proliferator-Activated Receptors
- Eicosanoids and Hypertension Pharmacology
- Mitochondrial Function and Pathology
Queen's University Belfast
2016-2025
University of Plymouth
2020
Auburn University
2020
Griffith University
2020
British Cardiovascular Society
2018-2020
Nestlé (France)
2020
King's College London
2003-2017
British Heart Foundation
2010-2017
Centre of Experimental Medicine of the Slovak Academy of Sciences
1998-2015
Royal Victoria Hospital
2010-2013
Increased reactive oxygen species (ROS) production is implicated in the pathophysiology of left ventricular (LV) hypertrophy and heart failure. However, enzymatic sources myocardial ROS are unclear. We examined expression activity phagocyte-type NADPH oxidase LV myocardium an experimental guinea pig model progressive pressure-overload hypertrophy. Concomitant with development hypertrophy, NADPH-dependent O2- homogenates, measured by lucigenin (5 micro mol/L) chemiluminescence or cytochrome c...
Cardiac failure occurs when the heart fails to adapt chronic stresses. Reactive oxygen species (ROS)-dependent signaling is implicated in cardiac stress responses, but role of different ROS sources remains unclear. Here we report that NADPH oxidase-4 (Nox4) facilitates adaptation stress. Unlike other Nox proteins, Nox4 activity regulated mainly by its expression level, which increases cardiomyocytes under stresses such as pressure overload or hypoxia. To investigate functional during...
Increased production of reactive oxygen species (ROS) is implicated in the development left ventricular hypertrophy (LVH). Phagocyte-type NADPH oxidases are major cardiovascular sources ROS, and recent data indicate a pivotal role gp91phox-containing oxidase angiotensin II (Ang II)-induced LVH. We investigated this pressure-overload gp91phox-/- mice matched controls underwent chronic Ang infusion or aortic constriction. II-induced increases activity, atrial natriuretic factor (ANF)...
Objective— Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) a ROS-generating enzyme expressed endothelium, levels which increase pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H 2 O ), but its role vivo remains unclear. Methods and Results— We generated transgenic mice with endothelium-targeted Nox4 overexpression (Tg) to study Nox4. Tg demonstrated...
Angiotensin (ANG) II (AngII) and aldosterone contribute to the development of interstitial cardiac fibrosis. We investigated potential role a Nox2-containing NADPH oxidase in aldosterone-induced fibrosis involvement this mechanism AngII-induced effects. Nox2-/- mice were compared with matched wild-type controls (WT). In WT mice, subcutaneous (s.c.) AngII (1.1 mg/kg/day for 2 wk) significantly increased activity, (11.5+/-1.0% vs. 7.2+/-0.7%; P<0.05), expression fibronectin, procollagen I,...
Oxidative stress plays an important role in the development of cardiac remodeling after myocardial infarction (MI), but sources oxidative remain unclear. We investigated Nox2-containing reduced nicotinamide-adenine dinucleotide phosphate oxidase MI. Adult Nox2(-/-) and matched wild-type (WT) mice were subjected to coronary artery ligation studied 4 weeks later. Infarct size MI was similar WT mice. exhibited significantly less left ventricular (LV) cavity dilatation dysfunction than (eg,...
Doxorubicin is a highly effective cancer treatment whose use severely limited by dose-dependent cardiotoxicity. It well established that doxorubicin increases reactive oxygen species (ROS) production. In this study, we investigated contributions to cardiotoxicity from Nox2 NADPH oxidase, an important ROS source in cardiac cells, which known modulate several key processes underlying the myocardial response injury. Nox2-deficient mice (Nox2-/-) and wild-type (WT) controls were injected with...
Abstract A key component of cardiac ischemia–reperfusion injury (IRI) is the increased generation reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study, we hypothesized that oxidative stress, due ischemia–reperfusion, induces senescence which contributes pathophysiology IRI. We demonstrate IRI cellular both cardiomyocytes interstitial cell populations treatment with senolytic drug...
In addition to its' established metabolic and cardioprotective effects, glucagon-like peptide-1 (GLP-1) reduces post-infarction heart failure via preferential actions on the extracellular matrix (ECM). Here, we investigated whether GLP-1 mimetic, exendin-4, modulates cardiac remodelling in experimental diabetes by specifically targeting inflammatory/ECM pathways, which are characteristically dysregulated this setting. Adult mice were subjected streptozotocin (STZ) infused with...
Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities reactive oxygen species (ROS) resultant damage to enzymes considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium several tissues under ischemic conditions vivo...
Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) iPS cell-derived ECs when exposed to hyperglycemia, and human iPS-ECs from patients. QKI-7 is also highly expressed coronary arterial donors, on blood vessels critical limb ischemia patients undergoing lower-limb amputation. expression tightly controlled by RNA splicing factors CUG-BP hnRNPM through direct binding. correlated with disrupted...
Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation. In experimental left ventricular hypertrophy (LVH), this endothelium-dependent LV relaxant response is impaired despite a preserved to exogenous NO. We investigated the potential role of reactive oxygen species (ROS) in defect.Short-term treatment with antioxidants vitamin C (10 micromol/L) or deferoxamine (500 restored responses NO agonists bradykinin nmol/L) and substance P (100 isolated ejecting hearts...
Gram negative endotoxemia is associated with an intrinsic impairment of cardiomyocyte contraction, in part due to a reduction myofilament Ca2+ responsiveness. Endotoxemic rat hearts show increased cardiac troponin I (cTnI) phosphorylation at serines 23 and 24, residues required for the protein kinase A (PKA)-dependent sensitivity after beta-adrenoceptor stimulation. To investigate functional significance TnI endotoxemia, we studied contractile effects systemic bacterial lipopolysaccharide...