Cardiovascular & Hormonal Research Laboratory

Lab head: Dr Anastasia Susie Mihailidou
Location: Lvl 13, Kolling Building, Royal North Shore Hospital

The Cardiovascular & Hormonal Research (CHR) Laboratory is part of the Kolling Institute of Research and we are located on Level 13 of the Kolling building at Royal North Shore Hospital. The research conducted is both clinical and experimental and the focus the pathophysiology of steroid hormones during diabetes and also hypertension. The laboratory is equipped with both physiological and electrophysiological equipment to investigate cellular mechanisms and how these translate to functional regulation and has access to the facilties for histological, molecular and biochemical assays. 
Heart disease is the leading cause of death in Australia, with ischemic heart disease a major cause of morbidity and mortality. Although thrombolytic therapy and percutaneous coronary interventions reduce mortality from acute myocardial infarction (MI), additional therapeutic strategies are needed. Clinical trials have shown low doses of mineralocorticoid receptor blockade administered to patients with heart failure decreased morbidity and mortality versus standard care alone, despite starting levels of plasma aldosterone in the low/normal range, raising the question of exactly what is the mechanism for the cardioprotective action of MR antagonists. The CHR Laboratory have provided important advances into defining the mechanism(s) involved in regulation of mineralocorticoid receptors in the heart and recognised nationally and internationally. The knowledge generated by our research studies has radically changed assumptions that mineralocorticoid receptors are uniquely an aldosterone receptor, and that any instance of activation of these receptors necessarily involves aldosterone.
Diabetes is the fastest growing disease worldwide, with increased mortality and morbidity resulting from the cardiovascular complications. Hyperglycemia has been shown to correlate closely with poor outcomes following acute myocardial infarction (AMI). The relationship between aldosterone and glucose metabolism is poorly explored. The group is currently investigating the mechanisms involved. There are also opportuinites for clinical research with Dr Mihailidou having established collaborations, to translate the findings to clinical management. 

Lab members: Dr Mahidu Mardini Dr Vincent Wong Mr Harris Mihailidis
Research approach equipment: We use established techniques which include Langendorff apparatus for the ischaemia-reperfusion studies, electrophysiology workstations for patch-clamping heart cells and also have access to histology equipment for immunohistochemistry and biochemical techniques and cell culture.

Le TYL, Ashton AW, Mardini M, Stanton PG, Funder JW, Handelsman DJ, Mihailidou AS (2014). Role of androgens in sex differences in cardiac damage during myocardial infarction. Endocrinology. 155: 568-575.

Mihailidou AS, Ashton AW (2014). “Cardiac effects of Aldosterone: does Gender matter?” in Special Issue: Extrarenal actions of aldosterone (mineralocorticoid receptor) (C Gomez-Sanchez, Series Editor). Steroids   (In Press, August 2014).

Leung M, Wong VW, Heritier S, Mihailidou AS,  Leung DY (2013). Rationale and design of a randomized trial on the impact of aldosterone antagonism on cardiac structure and function in diabetic cardiomyopathy. Cardiovascular Diabetology12: 139.

Phillips CL, Grunstein RR,  Darendeliler MA, Mihailidou AS, Srinivasan VK, Yee BJ, Marks GB, Cistulli PA (2013). Comparison of Health Outcomes of CPAP versus Oral Appliance Treatment for Obstructive Sleep Apnea: A Randomised Controlled Trial. American Journal of Respiratory and Critical Care Medicine. 187: 879-887.

Ohkubo T, Mihailidou AS (2013). Is there a role for Day-to-day home blood pressure variability in guiding management of hypertension. Frontiers in Research Series in Clinical & Experimental Physiology & Pharmacology, ( In Press, Sep 2013).

Young MJ, Fuller PJ, Stowasser M, Mihailidou AS (2013). Frontiers in Research Review: Aldosterone and Salt: Heart and Kidney. Clinical and Experimental Pharmacology and Physiology.40: 872–875.

AS Mihailidou, R Ritchie, AW Ashton  (2013). Sex Differences in Sudden Cardiac Death; In: Ischemic Heart Disease. Dr. David Gaze (Ed), ISBN 978-953-51-0993-8.  InTech - Open Access Publisher.

AS Mihailidou (2012). "Aldosterone in Heart Disease" in Special Issue: Hypertension: Kidney, Sodium, and Renin-Angiotensin (R Carey & A Mimran, Section Editors). Current Hypertension Reports. 14: 125-129.

AS Mihailidou(2012). Ischemic Heart Disease, Diabetes and Mineralocorticoid Receptors; In: Novel Strategies in Ischemic Heart Disease, Umashankar Lakshmanadoss (Ed.), ISBN: 978-953-51-0184-0.

Buckley T, Stannard A, Bartrop R, McKinley S, Ward C, Mihailidou AS, Morel-Kopp M-C, Spinaze M, Stannard A, Tofler G (2012). Effect of Early Bereavement on Heart Rate and Heart Rate Variability. American Journal of Cardiology. 110: 1378 –1383.

Le L, Mardini M, Howell, V, Funder JW, Ashton AW, Mihailidou AS (2012). Low dose spironolactone prevents ARC (Apoptosis Repressor with a Caspase-recruitment domain) degradation during myocardial infarction. Hypertension. 59:1164-1169.

Head GA, McGrath BP, Mihailidou AS, Nelson MR, Schlaich MP, Stowasser M, Mangoni AA, Cowley D, Brown MA, Ruta L-A, Wilson J (2012). Ambulatory blood pressure monitoring in Australia: 2011 consensus position statement. Journal of Hypertension 30:253–266.

Buckley T, Morel-Kopp M-C, Ward C, Bartrop R, McKinley S, Mihailidou AS, Spinaze M, Chen W, Tofler G  (2012). Inflammatory and Thrombotic Changes in Early Bereavement: a Prospective Evaluation. European Journal of Preventative Cardiology. Oct;19(5): 1145-1152.

Head GA, McGrath BP, Mihailidou AS, Nelson MR, Schlaich MP, Stowasser M, Mangoni AA, Cowley D, Brown MA, Ruta L-A, Wilson J (2011). What is ambulatory Blood Pressure Monitoring? Australian Family Physician  40:877-880.

Buckley T, Mihailidou AS, Bartrop R, McKinley S, Ward C, Morel-Kopp M-C, Spinaze M, Hocking B, Tofler G (2011). Hemodynamic changes during early bereavement: Potential contribution to increased cardiovascular risk. Heart Lung Circ. 20:91-98.  

Wong V, Mardini M, Cheung W, Mihailidou AS (2011). High dose insulin in experimental myocardial infarction in rabbits: protection against effects of hyperglycaemia. Journal of Diabetes and Its Complications,25:122-128.

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)

Head G, Mihailidou AS, 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: Anastasia 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). 

Discipline: Pathology
Co-supervisors: Anthony Ashton
Keywords: Redox biochemistry, Molecular biology, Cardiovascular diseases