Understanding The Cardio-protective Actions Of The AT2R In Females: Shifting Gears Between AT1 And AT2 Receptor Balance Of Function With Relaxin.
Funder
National Health and Medical Research Council
Funding Amount
$1,049,288.00
Summary
Women are protected from cardiovascular disease as compared to age-matched men, an effect lost with age. Understanding protective factors that act in females could be used to treat hypertension, heart failure and stroke in males at all ages, and maintain protection in elderly women. Our studies aim to determine if relaxin, an ovarian hormone, can promote cardiovascular health in women.
Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Preclinical Relaxin Therapy To Reverse Cardiac Fibrosis And Gain Functional Benefits
Funder
National Health and Medical Research Council
Funding Amount
$724,754.00
Summary
Cardiac fibrosis is a key factor promoting heart disease and onset of complications including arrhythmias and heart failure. There is urgent and unmet need of drugs that can reverse fibrosis. By documenting anti-fibrotic action of a peptide hormone relaxin, CIA and his team will test therapeutic effect of relaxin in heart disease models focusing on fibrosis-reversal and functional gain, particularly arrhythmias. This work would promote development of relaxin as a new cardiovascular drug.
This project will substantially improve our understanding of the potential causes of vascular complications of pregnancy including preeclampsia, and provide a solid foundation to develop new clinical interventions for women who develop this disease during their pregnancy. It will also investigate if a peptide hormone, relaxin, could be an effective treatment to manage the health of women diagnosed with preeclampsia during their pregnancy and prevent delivery of severely premature infants.