A5001527769- Nitric Oxide and Endothelin Effects
- Pulmonary Hypertension Research and Treatments
- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Renin-Angiotensin System Studies
- Lipoproteins and Cardiovascular Health
- Eicosanoids and Hypertension Pharmacology
- Heart Failure Treatment and Management
- Angiogenesis and VEGF in Cancer
- Adenosine and Purinergic Signaling
- Cardiovascular Issues in Pregnancy
- Cardiovascular Function and Risk Factors
- Receptor Mechanisms and Signaling
- Hormonal Regulation and Hypertension
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer, Lipids, and Metabolism
- Diet and metabolism studies
- Cardiac, Anesthesia and Surgical Outcomes
- Caveolin-1 and cellular processes
- Mitochondrial Function and Pathology
- Neuropeptides and Animal Physiology
- Cerebrovascular and Carotid Artery Diseases
- Gestational Diabetes Research and Management
- Redox biology and oxidative stress
- Ion Transport and Channel Regulation
Australian Regenerative Medicine Institute
2017-2024
Monash University
2007-2024
Victorian Heart Hospital
2024
The University of Sydney
2016-2023
Australian Centre for Heart Health
2023
Royal North Shore Hospital
2017-2022
William Harvey Research Institute
2012-2019
Queen Mary University of London
2012-2019
Keogh Institute for Medical Research
2016
Barts Health NHS Trust
2014
Elevation of circulating nitrite (NO2(-)) levels causes vasodilatation and lowers blood pressure in healthy volunteers. Whether these effects the underpinning mechanisms persist hypertension is unknown. Therefore, we investigated consequences systemic elevation spontaneously hypertensive rats conducted proof-of-principle studies patients. Nitrite caused dose-dependent pressure-lowering that was profoundly enhanced versus normotensive Wistar Kyoto controls. This effect virtually abolished by...
The endothelium plays a fundamental role in maintaining vascular homeostasis by releasing factors that regulate local blood flow, systemic pressure, and the reactivity of leukocytes platelets. Accordingly, endothelial dysfunction underpins many cardiovascular diseases, including hypertension, myocardial infarction, stroke. Herein, we evaluated mice with endothelial-specific deletion Nppc, which encodes C-type natriuretic peptide (CNP), determined this mediator is essential for multiple...
There is now extensive evidence suggesting that intrauterine perturbations are linked with an increased risk of developing cardiovascular disease. Human epidemiological studies, supported by animal models, have demonstrated association between low birth weight, a marker growth restriction (IUGR), and adult However, little known the early influence IUGR on fetal heart vessels. The aim this study was to determine effects late gestational coronary artery function cardiomyocyte maturation in...
Angiogenesis and vascular remodeling are complementary, innate responses to ischemic cardiovascular events, including peripheral artery disease myocardial infarction, which restore tissue blood supply oxygenation; the endothelium plays a critical function in these intrinsic protective processes. C-type natriuretic peptide (CNP) is fundamental endothelial signaling species that coordinates homeostasis. Herein, we sought delineate central role for CNP angiogenesis response ischemia.The vitro...
Pulmonary hypertension (PH) is a life-threatening disorder characterized by increased pulmonary artery pressure, remodeling of the vasculature, and right ventricular failure. Loss endothelium-derived nitric oxide (NO) prostacyclin contributes to PH pathogenesis, current therapies are targeted restore these pathways. Phosphodiesterases (PDEs) family enzymes that break down cGMP cAMP, which underpin bioactivity NO prostacyclin. PDE5 inhibitors (eg, sildenafil) licensed for PH, but role PDE2 in...
Spheroid cultures are among the most explored cellular biomaterials used in cardiovascular research, due to their improved integration of biochemical and physiological features heart a defined architectural three-dimensional microenvironment when compared monolayer cultures. To further explore potential use spheroid for we engineered novel vitro model with vascularized cardiac spheroids (VCSs), by coculturing myocytes, endothelial cells, fibroblasts isolated from dissociated rat neonatal...
TRPV1 is a member of the transient receptor potential ion channel family and gated by capsaicin, pungent component chili pepper. It expressed predominantly in small diameter peripheral nerve fibers activated noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) cytochrome P-450 4A/4F-derived metabolite membrane phospholipid arachidonic acid. powerful vasoconstrictor has structural similarities with other agonists, e.g. hydroperoxyeicosatetraenoic 12-HPETE, we hypothesized...
Significance The morbidity and mortality associated with heart failure (HF) are unacceptably high. Cyclic guanosine-3′,5′-monophosphate (cGMP) plays a key role in preserving cardiac structure function, therapeutically targeting cGMP HF has shown promise experimental models patients. Phosphodiesterases (PDEs) metabolize curtail the actions of (and cAMP), increased PDE activity is thought to contribute pathogenesis. Herein, we show that inhibition one specific isoform, PDE2, enhances salutary...
Introduction Coronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification treatment traditional risk factors. Data emerging over the past decade show quarter patients have in absence any known factor, half only one factor. Improvements quantification characterisation coronary atherosclerosis by CT angiography (CTCA) can provide quantitative measures subclinical atherosclerosis—enhancing power unbiased ‘omics’ studies to unravel...
Preeclampsia is a cardiovascular pregnancy complication characterised by new onset hypertension and organ damage or intrauterine growth restriction. It one of the leading causes maternal fetal mortality in globally. Short pre-term delivery fetus placenta, treatment options are limited. Consequently, preeclampsia leads to increased disease risk both mothers offspring later life. Here we aim examine impact reduced uterine perfusion pressure (RUPP) rat model on system, placental heart...
Previous studies have shown that intrauterine growth restriction (IUGR) can impair nephrogenesis, but uncertainties remain about the importance of gestational timing insult and effects on renal renin-angiotensin system (RAS). We therefore hypothesized induction IUGR during late gestation alters RAS, this is associated with a decrease in nephron endowment. Our aims were to determine induced later stages nephrogenesis 1) number; 2) mRNA expression angiotensin AT(1) AT(2) receptors,...
Early life environmental influences can have lifelong consequences for health, including the risk of cardiovascular disease. Uteroplacental insufficiency causes fetal undernutrition and impairs growth. Previously we shown that uteroplacental is associated with impaired maternal mammary development, compromising postnatal growth leading to hypertension in male rat offspring. In this study investigated roles prenatal nutritional environments on endothelial smooth muscle reactivity passive wall...
Pre-menopausal females have a lower incidence of cardiovascular disease compared with age-matched males, implying differences in the mechanisms and pathways regulating vasoactivity. In small arteries, myogenic tone (constriction response to raised intraluminal pressure) is major determinant vascular resistance. Endothelium-derived dilators, particularly NO, tonically moderate and, because endothelium an important target for female sex hormones, we investigated whether NO-mediated moderation...
Many studies report sexual dimorphism in the fetal programming of adult disease. We hypothesized that there would be differences age-related decline renal function between male and female intrauterine growth-restricted rats. Early-life growth restriction was induced rat offspring by administering a low-protein diet (LPD; 8.7% casein) to dams during pregnancy lactation. Control were fed normal-protein (NPD; 20% casein). Mean arterial pressure (MAP) structure assessed 32- 100-wk-old offspring....
Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk future and metabolic disorders. Much the pathogenesis mechanisms involved in cardiac health preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, emerging as having potential role both disease (CVD). Therefore, this study we aimed characterise FKBPL regulation rat reduced uterine perfusion pressure (RUPP) 3D spheroid model preeclampsia.The RUPP was induced pregnant rats histological...
This study demonstrates the therapeutic potential for right-sided heart failure of a novel inhibitor P2X7 receptor (P2X7R). Inflammatory signaling and right ventricular function were improved in mouse model pulmonary fibrosis with secondary hypertension when treated this inhibitor. Importantly, survival was also improved, suggesting that inhibitor, other P2X7R antagonists, could be uniquely effective ventricle (RV)-targeted therapy hypertension. addresses major limitation current treatment...