Aldosterone mediated cardiac pathophysiology:The role of corticosteroid receptors and 11 HSD isoforms

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/268919

Funding Status
Closed

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Funded Activity Summary

Aldosterone a hormone that circulates in blood and is associated with cardiovascular disease. Recently, two clinical trials (RALES, EPHUSUS) demonstrate that if you stop this hormone from acting by giving drugs that inhibit it from binding to the receptor that mediates its response, there is an improvement in the health of heart failure patients. How aldosterone mediates its detrimental effects on heart is largely unknown. Glucocorticoids are another hormone that circulates in blood and can bind to the same receptor as aldosterone. In contrast to aldosterone glucocorticoids appear to play a basic maintenance role in heart. Our central hypothesis is that in the healthy heart aldosterone has minimal effects , however, in the diseased heart aldosterone associated pathophysiology is a result of both an increase in the ability of aldosterone to signal to cells and disruption of glucocorticoid signalling. This grant proposal will address how aldosterone and glucocorticoids may directly signal within cardiac cells and how this signalling changes in the diseased heart. In addition, we investigate if enzymes that metabolize glucocortioids and thus render them non-functional play a role in cardiac disease, and if we can reverse the detrimental effects of aldosterone by artificially increasing the production of glucocorticoids in heart. By understanding the mechanisms by which aldosterone promotes cardiac disease, and the role of glucocorticoids and their metabolism in this process will lead to a better understanding of aldosterone induced pathology and thus lead to novel therapeutic targets.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $481,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Nutritional science

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

11-beta hydroxysteroid dehydrogenase | Aldosterone | Cardiac fibrosis | Cardiac hypertrophy | cardiovascular disease and hypertension | cell signalling | glucocorticoid receptor | mineralocorticoid receptor | molecular mechanisms

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