A5056680008- Caveolin-1 and cellular processes
- Nitric Oxide and Endothelin Effects
- Atherosclerosis and Cardiovascular Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Advanced Glycation End Products research
- Inflammasome and immune disorders
- Eicosanoids and Hypertension Pharmacology
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Cardiovascular Function and Risk Factors
- Peroxisome Proliferator-Activated Receptors
- Genomics, phytochemicals, and oxidative stress
- Ion Transport and Channel Regulation
- Muscle Physiology and Disorders
- ATP Synthase and ATPases Research
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Mitochondrial Function and Pathology
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Pancreatic function and diabetes
- Nuclear Receptors and Signaling
- Cholesterol and Lipid Metabolism
Monash University
2019-2024
Baker Heart and Diabetes Institute
2014-2023
St. Paul's Hospital
2009-2015
University of British Columbia
2009-2015
St. Paul's Hospital
2014
Diabetes Australia
2012
University of Victoria
2011
Lung Institute
2010
Aberrant regulation of eNOS and associated NO release are directly linked with various vascular diseases. Caveolin-1 (Cav-1), the main coat protein caveolae, is highly expressed in endothelial cells. Its scaffolding domain serves as an endogenous negative regulator function. Structure-function analysis Cav-1 has shown that phenylalanine 92 (F92) critical for inhibitory actions toward eNOS. Herein, we show F92A–Cav-1 a mutant cell–permeable peptide called Cavnoxin can increase basal...
Low-grade persistent inflammation is a feature of diabetes-driven vascular complications, in particular activation the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome to trigger maturation and release inflammatory cytokine interleukin-1β (IL-1β). We investigated whether inhibiting NLRP3 inflammasome, through use specific small-molecule inhibitor MCC950, could reduce inflammation, improve function, protect against diabetes-associated atherosclerosis...
Oxidative stress and inflammation are inextricably linked play essential roles in the initiation progression of diabetes complications such as diabetes-associated atherosclerosis nephropathy. Bolstering antioxidant defenses is an important mechanism to lessen oxidative inflammation. In this study, we have used a novel analog NFE2-related factor 2 (Nrf2) agonist bardoxolone methyl, dh404, investigate its effects on diabetic macrovascular renal injury streptozotocin-induced apolipoprotein...
Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to dysfunction. Nrf2, master regulator several anti-oxidant genes suppressor inflammatory NF-κB, has potential as target combat inflammation. The aim this study was investigate effects novel Nrf2 activator, bardoxolone methyl derivative dh404, on endothelial function vitro vivo. dh404 at 3 mg/kg administered male Akita mice, an...
Patients with diabetes have an increased risk of developing atherosclerosis. Endothelial dysfunction, characterized by the lowered bioavailability endothelial NO synthase (eNOS)–derived NO, is a critical inducer However, protective aspect eNOS in diabetes-associated atherosclerosis remains controversial, likely consequence its capacity to release both or deleterious oxygen radicals normal and disease settings, respectively. Harnessing atheroprotective activity diabetic settings elusive, part...
Nanoporous metal-phenolic particles are fabricated through the nanostructural replication of dense FeIII -TA complexes in nanoporous CaCO3 template particles. The have potential for diagnostic detection endogenous levels H2 O2 ex vivo and by ultrasound imaging, which is based on catalytic activity coordinated Fe3+ to break down microbubbles.
Abstract Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been reported in diabetic complications including kidney disease (DKD). However, it remains unknown if NLRP3 inhibition is renoprotective a clinically relevant interventional approach with established DKD. We therefore examined the effect NLRP3-specific inhibitor MCC950 streptozotocin-induced mice to measure impact on renal inflammation and associated pathology...
Myoferlin is a member of the ferlin family proteins that promotes endomembrane fusion with plasma membrane in muscle cells and endothelial cells. In addition, myoferlin necessary for surface expression vascular growth factor receptor 2 through formation protein complex dynamin-2 (Dyn-2). Since Dyn-2 fission endocytic vesicles from membrane, we tested hypothesis may regulates aspects receptor-dependent endocytosis. Here show gene silencing decreases both clathrin caveolae/raft-dependent...
Cardiovascular complications associated with diabetes remain a significant health issue in westernized societies. Overwhelming evidence from clinical and laboratory investigations have demonstrated that these cardiovascular are initiated by dysfunctional vascular endothelium. Indeed, endothelial dysfunction is one of the key events occur during diabetes, leading to acceleration mortality morbidity. In diabetic milieu, occurs as result attenuated production derived nitric oxide (EDNO)...
Ferlins are known to regulate plasma membrane repair in muscle cells and linked muscular dystrophy cardiomyopathy. Recently, using proteomic analysis of caveolae/lipid rafts, we reported that endothelial (EC) express myoferlin it regulates expression vascular growth factor receptor 2 (VEGFR-2). The goal this study was document the presence other ferlins EC.EC expressed another ferlin, dysferlin, contrast myoferlin, did not VEGFR-2 levels or downstream signaling (nitric oxide Erk1/2...
Metabolic conditions such as obesity, insulin resistance and glucose intolerance are frequently associated with impairments in skeletal muscle function metabolism. This is often linked to dysregulation of homeostatic pathways including an increase reactive oxygen species (ROS) oxidative stress. One the main sites ROS production mitochondria, where flux substrates through electron transport chain (ETC) can result generation free radicals. Fortunately, several mechanisms exist buffer bursts...
The increasing burden of heart failure globally can be partly attributed to the increased prevalence diabetes, and subsequent development a distinct form known as diabetic cardiomyopathy. Despite this, effective treatment options have remained elusive, due lack an experimental model that adequately mimics human disease. In current study, we combined three consecutive daily injections low-dose streptozotocin with high-fat diet, in order recapitulate long-term complications specific focus on...
Despite advances in treatment, atherosclerotic cardiovascular disease remains the leading cause of death patients with diabetes. Even when risk factors are mitigated, progresses, and thus, newer targets need to be identified that directly inhibit underlying pathobiology atherosclerosis A single-cell sequencing approach was used distinguish proatherogenic transcriptional profile aortic cells diabetes using a streptozotocin-induced diabetic Apoe-/- mouse model. Human carotid endarterectomy...
Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb), have been tested in vitro studies for their ability to scavenge reactive oxygen and nitrogen species, hydrogen peroxide peroxynitrite. In this study, we investigated the efficacies of two Eb analogues, m-hydroxy (ME) ethanol-ebselen (EtE) compared these with cell based assays. We found that ME is superior attenuating activation peroxide-induced pro-inflammatory mediators, ERK P38 human aortic endothelial cells....
The members of the BCL-2 family are crucial regulators mitochondrial pathway apoptosis in normal physiology and disease. Besides their role cell death, proteins have been implicated regulation oxidative phosphorylation cellular metabolism. It remains unclear, however, whether these a physiological glucose homeostasis metabolism vivo. In this study, we report that fat accumulation liver increases c-Jun N-terminal kinase–dependent interacting mediator death (BIM) expression hepatocytes. To...