Cardiovascular & Hormonal Research Laboratory
Lab head: Dr Anastasia Susie Mihailidou
Location: Lvl 13, Kolling Building, Royal North Shore Hospital
Lab members: Ms Loan Le Dr Mahidu Mardini Dr Vincent Wong Mr Harris Mihailidis
Funding: National Heart Foundation & North Shore Heart Research Foundation
Research approach equipment: We will use established techniques in our laboratories recently relocated to the Kolling Building. These include Langendorff apparatus for the ischaemia-reperfusion studies, electrophysiology workstations for patch-clamping heart cells and access to equipment to measure molecular changes.
Buckley T, Mihailidou AS, Bartrop R, McKinley S, Ward C, Morel-Kopp M-C, Spinaze M, Hocking B, Tofler G. Increased blood pressure and heart rate during early bereavement: Potential mechanism of increased cardiovascular risk (submitted Heart Lung & Circulation 2010)
Buckley T, Morel-Kopp M-C, Ward C, Bartrop R, McKinley S, Mihailidou AS, Spinaze M, Chen W, Tofler G. Inflammatory and Thrombotic Changes in Early Bereavement: a Prospective Evaluation (submitted European Heart Journal 2010)
Wong V, Mardini M, Cheung W, Mihailidou AS. High dose insulin in experimental myocardial infarction in rabbits: protection against effects of hyperglycaemia.(In Press, Journal of Diabetes and Its Complications, 4 March2010)
Head G, MihailidouAS, Duggan K, Beilin LJ, BerryN, Brown MA, Bune A, Cowley D, Chalmers JP, Howe PRC, Hodgson J, Ludbrook J, Mangoni AA, McGrath BP, Morley CM, Nelson MR, Sharman JE, Stowasser M. Relationship between ambulatory and Clinic Blood Pressure: Defining diagnostic and treatment targets. (British Medical Journal, Online April 2010)
Mihailidou AS, Le TYL, Mardini M, Funder JW (2009). Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. Hypertension 54:1306-1312.
Funder JW, Mihailidou AS (2009). Aldosterone and mineralocorticoid receptors: Clinical studies and basic biology. Mol Cell Endocrinol 301: 2-6.
Buckley T, Bartrop R, McKinley S, Ward C, Bramwell M, Roche D, Mihailidou AS, Morel-Kopp M-C, Spinaze M, Hocking B, Goldston K, Tennant C, Tofler G. (2009). A Prospective study of early bereavement on psychological and behavioural cardiac risk factors. Internal Med J 39: 370-378.
Mihailidou AS (2006). Nongenomic actions of aldosterone: Physiological or pathophysiological role? Steroids 71: 277-280.
Mihailidou AS, Funder JW (2005). Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system. Steroids 70: 347-351.
Mihailidou AS (2005). Review: Nongenomic cardiovascular actions of aldosterone: a receptor for all seasons? Endocrinology 146: 971-972.
Mihailidou AS, Mardini M and Funder JW (2004). Rapid, non-genomic effects of aldosterone in the heart medicated by ePKC. Endocrinology 145: 773-780.
Regulation of aldosterone/mineralocorticoid receptors in the heart
Primary supervisor: Susie Mihailidou
Ischemic heart disease remains the leading cause of death worldwide. Following the ischemic event, reperfusion triggers generation of reactive oxygen species and impairs myocardial antioxidant defences, leading to further cardiac damage. High plasma aldosterone levels during percutaneous coronary intervention double the risk of mortality. Inappropriately elevated levels of aldosterone produce cardiac and vascular inflammation and fibrosis, via activation of mineralocorticoid receptors. Clinical trials show that low doses of mineralocorticoid receptor antagonists added to standard treatment increase survival and decrease hospitalization. Since free circulating levels of cortisol are 100-fold higher than aldosterone levels, mineralocorticoid receptors bind both aldosterone and cortisol with equal affinity. Our recent studies show that during myocardial ischemia-reperfusion, cardiac damage is aggravated by activation of mineralocorticoid receptors by both aldosterone and cortisol. We have recently identified that blockade of these receptors prevents cardiac damage and this project will determine the mechanisms involved. The studies will involve both functional studies and molecular techniques (immunohistochemistry, western blot analysis).
Co-supervisors: Anthony Ashton
Keywords: Redox biochemistry, Molecular biology, Cardiovascular diseases