We are interested in the regulation of vascular tone, the influence of disease on vascular reactivity and potential pharmacological strategies to improve vascular function.
- Ms Saher Ali - PhD Student
- Ms Salheen Salheen - PhD Student
- Ms Kai Yee Chin - PhD Student
- Mr Bill Darby - PhD Student, with Peter McIntyre
- Mr Omar Al Zahrani - PhD Student, with Peter McIntyre
- Mr Christopher Seaman, Honours Student
- Ms Suzan Yildiz, Honours Student
- Dr Clive May, Howard Florey Institute
- Dr Colleen Thomas, Howard Florey Institute
- Prof Bevyn Jarrott, Howard Florey Institute
- Dr Rebecca Ritchie, Baker Heart Research Institute
- Prof Mike Hill, University of Missouri
We have a number of ongoing research projects investigating cardiovascular physiology and pharmacology.
Flavonoids are polyphenolic compounds that are found in fruits and vegetables. In populations with a diet high in fruits and vegetables there is a lower incidence of coronary artery disease and that effect has been linked to the beneficial actions of flavonoids. We are examining the mechanism of the vasodilator actions of flavonoids and their ability to prevent diabetes-induced and ischaemia-induced cardiovascular dysfunction.
Our studies thus far suggest that flavonols are able to inhibit the utilisation of calcium leading to smooth muscle relaxation but that this occurs only at relatively high concentrations. At lower concentrations, the flavones and flavonols exert antioxidant effects that lead to enhanced NO-mediated dilatation.
The vascular endothelium is an important source of powerful vasodilators such as NO, endothelium-derived hyperpolarising factor (EDHF) and prostacyclin (PGI2). The relative importance of these agents in regulating blood flow to the heart and other organs may be influenced by coronary artery disease. We have demonstrated that upon reintroduction of blood flow to a vascular bed that has been ischaemic (no blood flow) for some time there is a reduction in resting blood flow, in comparison to pre-ischaemic levels, and an impaired ability of the arteries to respond to vasodilator drugs. That vessel dysfunction may be due to damage to the endothelium or accumulation of leukocytes (white blood cells) that attach to the endothelium and block blood flow.
In collaboration with Drs May and Thomas at the Howard Florey Institute, we are investigating the effects of myocardial ischaemia and reperfusion on cardiac and coronary vascular function. This work has led to the establishment of the start-up company, NeuProtect Pty Ltd, with work continuing in the Vascular Pharmacology Laboratory and at the Howard Florey Institute. Investigation into the synthesis of new flavonoids that will optimize the beneficial actions of the naturally occurring compounds is being conducted in collaboration with Dr Spencer Williams and Dr Tony Hughes from the University of Melbourne. Novel synthetic flavonols are being used to investigate the mechanism by which these compounds may improve cardiovascular function in diabetes or after myocardial infarction (heart attack).
A major recent focus for our work is the effect of diabetes on endothelial function and the potential for flavonols to preserve endothelial function in the face of diabetes-induced oxidant stress. Diabetes is a major risk factor for vascular disease and we are investigating the pathological processes resulting from high glucose levels that result in vascular dysfunction to try to identify targets for drug intervention.
Dr Hart’s main scientific research interest is to examine novel signaling mechanisms in blood vessel regulation. Although her work covers both large and small blood vessels, she is particularly interested in the regulation of small resistance-like vessels, which are important for the regulation of blood pressure and blood flow to organs. These vessels are dysfunctional in states of vascular disease, like hypertension, diabetes and atherosclerosis and she is interested in unraveling the reasons for this dysfunction, as well as further understanding the normal physiology of these vessels. In the past few years most of her work has focused on the role of the biological gas, hydrogen sulfide (H2S) in regulation of blood vessels and its potential role in protecting the vasculature from the effects of oxidative stress. She is an expert in cardiovascular disease modeling, small blood vessel myography and she utilizes biochemical and molecular biology techniques in her research projects.
Together with Professor McIntyre, Professor Woodman and Dr Potocnik are investigating the role of the transient receptor potential channel TRPV4 in the regulation of small vessel tone with a particular focus on their interaction with G protein coupled receptors (GPCRs) and their contribution to the regulation of vascular tone by the shear forces generated by the flow of blood over the endothelial cells lining all blood vessels.
Dr Potocnik has special expertise in the investigation of microvessel physiology. In general, the ’basic’ microvascular preparation is an isolated arteriole (diameter about 100 µm) and these arterioles are studied in vitro. The function of arterioles is explored using video microscopy, fluorescent indicators and confocal microscopy on live functional arterioles or after they have been ’frozen/fixed’ in a particular state for biochemical or immunocytochemical analysis. Complementary studies of Ca2+ handling in the vasculature are performed using cultured cells such as endothelium and freshly dispersed smooth muscle. We are particularly interested in the contribution of smooth muscle phenotype and the actions of current therapeutics on arterioles in the development of hypertensive cardiovascular disease and in diabetes.
Why not join us?
All enquiries about joining us as honours and postgraduate students or as postdoctoral Fellows should be directed to Professor Owen Woodman.