Vascular Biology Research Group
In the Vascular Biology Research Group we are interested in the regulation of vascular tone, the influence of disease on vascular reactivity and potential pharmacological strategies to improve vascular function.
A major focus of our work is investigation of the potential of flavonoids to protect the cardiovascular system from injury as a result of their antioxidant and vasodilator activity.
Professor Owen Woodman
Research Group Leader
- Ms Anjali Joshi - PhD Student
- Ms Erin Stephenson - PhD Student, with Professor John Hawley
- Mr Chen Huei Leo - PhD Student
- Mr Sapha Mosawy - PhD Student, with Dr Matthew Linden
- 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
- Dr Spencer Williams, School of Chemistry, University of Melbourne
- Dr James Ziogas, Department of Pharmacology, University of Melbourne
- Australian Research Council
- National Heart Foundation
We have a number of ongoing research projects investigating the cardiovascular actions of different flavonoids together with the ability to prevent or reverse cardiovascular disease.
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 vascular dysfunction.
Our studies thus far suggest that flavones, flavonols and isoflavones upon acute administration 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. By contrast, chronic treatment with isoflavones may increase the activity of endothelial nitric oxide synthase (eNOS) enhancing endothelium-dependent vasodilatation.
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. 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 effects 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..
- Woodman OL, Boujaoude M. (2004) Chronic treatment of male rats with daidzein and 17-oestradiol induces the contribution of EDHF to endothelium-dependent relaxation. British Journal of Pharmacology, 141, 322-328; doi:10.1038/sj.bjp.0705603.
- Wang S, Dusting GJ, Woodman OL, May CN. (2004) Selective vasodilator and chronotropic actions of 3’,4’-dihydroxyflavonol in conscious sheep. European Journal of Pharmacology, 491, 43-51.
- Sobey CG, Weiler JM, Boujaoude M, Woodman OL. (2004) Effect of short-term phytoestrogen treatment in male rats on nitric oxide-mediated responses of cerebral arteries: comparison with 17-estradiol. Journal of Pharmacology and Experimental Therapeutics, 310, 135-140.
- Wang S, Dusting GJ, May CN, Woodman OL. (2004) 3’, 4’-Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep. British Journal of Pharmacology,142, 443-452.
- Woodman OL, Missen MA, Boujaoude M. (2004) Daidzein and 17-oestradiol enhance NOS activity associated with an increase in calmodulin and a decrease in caveolin-1. Journal of Cardiovascular Pharmacology, 44, 155-163.
- Woodman OL, Chan ECH. (2004) Vascular and antioxidant actions of flavones and flavonols. Clinical and Experimental Pharmacology and Physiology, 31, 786-790.
- Ritchie RH, Gordon, JM, Woodman OL, Cao AH, Dusting GJ. (2005) Annexin-1 peptide Anx-12-26 protects adult rat cardiac myocytes from cellular injury induced by simulated ischaemia. British Journal of Pharmacology, 145, 495-502.
- Woodman OL, Meeker WF, Boujaoude M. (2005) Vasorelaxant and antioxidant activity of flavonols and flavones: structure activity relationships. Journal of Cardiovascular Pharmacology, 46, 302-309.
- Garreffa AM, Woodman OL, Cao A, Ritchie, RH. (2006) Sodium nitroprusside protects adult rat cardiomyocytes from cellular injury induced by simulated ischemia: role for a non-cGMP-dependent mechanism of nitric oxide protection, Journal of Cardiovascular Pharmacology, 47, 1-8.
- Laskowski A, Woodman OL, Cao AH, Drummond GR, Marshall T, Kaye DM, Ritchie RH. (2006) Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes. Cardiovascular Research, 72, 112-123.
- Goh SSC, Woodman OL, Pepe S, Cao, AH, Qin C, Ritchie, RH. (2007) The red wine antioxidant resveratrol prevents cardiomyocyte injury following ischemia-reperfusion via multiple sites and mechanisms. Antioxidants & Redox Signaling, 9, 101-113
- Jackman KA, Woodman OL, Chrissobolis S, Sobey CG. (2007) Vasorelaxant and antioxidant activity of the isoflavone metabolite equol in carotid and cerebral arteries. Brain Research, 99-107.
- Jackman KA, Woodman OL, Sobey CG. (2007) Isoflavones, equol and cardiovascular disease: pharmacological and therapeutic insights. Current Medicinal Chemistry, 14, 2824-2830.
- Malakul W, Thirawarapan S, Suvitayavat W, Woodman OL. (2008) Type 1 diabetes and hypercholesterolaemia reveal the contribution of EDHF to endothelium-dependent relaxation of rat aorta. Clinical and Experimental Pharmacology and Physiology, 35, 192-200.
- Woodman OL. (2008) Editorial commentary: Oestrogen and vasculoprotection. Clinical and Experimental Pharmacology and Physiology, 35, 243-244.
- Qin C, Chen X, Hughes RA, Williams SJ, Woodman OL. (2008) Understanding the cardioprotective effects of flavonols: discovery of relaxant flavonols without antioxidant activity. Journal of Medicinal Chemistry, (published online 29 February 2008), doi:10.1021/jm070352h.
- Woodman OL, Malakul W, Cao AH, Xu Q, Ritchie RH. (2008) Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction. Life Sciences (published online 6 March 2008), doi:10.1016/j.lfs.2008.01.016.
- Yap S, Loft, KJ, Woodman OL, Williams SJ. (2008) Discovery of water soluble antioxidant flavonols without vasorelaxant activity. ChemMedChem, 3, 1572-1579.
- Woodman OL, Malakul W. (2009) 3’,4’-Dihydroxyflavonol prevents diabetes-induced endothelial dysfunction in rat aorta. Life Sciences, 85, 54-59.
- Mellor KM, Ritchie RH, Meredith G, Woodman OL, Morris MJ, Delbridge LMD. (2009) High fructose diet elevates myocardial superoxide generation in mice in the absence of cardiac hypertrophy. Nutrition, (in press, accepted August 2009).
- Qin CX, Yap S, Woodman OL. (2009) Antioxidants in the prevention of myocardial ischaemia/reperfusion injury. Expert Reviews in Clinical Pharmacology, 2, 673-695.
- Wang S, Thomas CJ, Dusting GJ, Woodman OL, May CN. (2009) 3', 4'- Dihydroxyflavonol improves post-ischemic coronary endothelial function after 7 days reperfusion in conscious sheep. European Journal of Pharmacology, 624, 31-37.
Why not join us?
All enquiries about joining the group as Honours and Postgraduate students or as Post-doctoral Fellows should be directed to Professor Owen Woodman.