EGF receptor transactivation in GPCR-mediated cardiac hypertrophy

Funded Activity Summary

Soon after birth, the muscle cells of the human heart stop dividing and subsequent growth of the heart occurs through enlargement of pre-existing muscle cells in a process referred to as hypertrophy. This normal growth accounts for the difference in size between juvenile and adult human hearts. In certain people, heart cell growth is accelerated as a consequence of complex genetic, hormonal and environmental factors. In others, it occurs as an adaptive response to high blood pressure or damage-disease of the heart muscle, such as occurs following a heart attack. As hearts grow inappropriately, they function less efficiently and eventually fail. Cardiac hypertrophy is therefore a major risk factor for heart failure and death. Hormones like adrenalin, angiotensin, and endothelin affect cells of the heart and blood vessels to regulate blood pressure and volume. In addition, these hormones also act directly on heart cells to cause growth, particularly during the accelerated phase associated with cardiac hypertrophy. One attribute shared by these hormones is that they act through G-protein coupled receptors (GPCRs), a superfamily of cell surface proteins. How binding of hormone to its specific GPCR triggers cell growth has been the focus of extensive research. Based on studies of angiotensin receptors in cultured muscle cells, we have observed that the growth action of angiotensin receptors requires them to first hijack another receptor - the epidermal growth factor receptor. By commandeering the EGF receptor, the angiotensin hormone in effect usurps growth-signalling pathways. This application proposes experiments that will investigate the mechanism and consequence of GPCRs stimulation of EGF receptors in heart cells and whole animals. By understanding the mechanism by which angiotensin promotes growth, better therapeutic regimens against abnormal growth of the heart during human cardiovascular disease will evolve.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $710,625.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Nutrigenomics and personalised nutrition

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

EGF receptor transactivation | G-protein coupled receptors | angiotensin II receptors | cardiac hypertrophy | cardiovascular disease and hypertension | cell signalling | heart disease | molecular mechanisms

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