Dr Morag Young
Our work has identified a hormone receptor (the MR) as a key player in heart disease - we now know MR can also regulate the heart tissue 'clock'. However, we don’t know how MR and this clock are connected. Using laboratory-based models, we aim to understand exactly how the MR works with the body clock to cause heart disease – this will then help us identify better and safer treatments for heart disease.
Identification of key downstream signalling mechanisms for the MR in the cardiovascular system will allow us to target MRAs with selective actions and fewer side effects.
Centre for Endocrinology and Metabolism
Journal and article title
This study is the first to demonstrate that the full development of MR-mediated cardiac inflammation and fibrosis is dependent upon intact signaling by the circadian protein, CLOCK.
Drugs that block the hormone receptor MR are effective therapy for heart failure, but aren’t commonly used due to their significant side effects. If we can determine specific interactions between MR and the heart 'clock', we can use this knowledge to improve upon existing MR antagonists or design new drugs without these side effects to effectively treat patients. Safer drugs may be used in younger patients over a longer period of time, reducing symptomatic heart failure and the burden of disease.
Other points of interest
The circadian clock, subject of this year’s Nobel Prize, is a tightly-controlled signalling system found in every cell. Local 'tissue clocks' are kept in time by signals (hormones) controlled by the central clock in the brain, which enables our body systems to anticipate environmental changes (e.g. day to night). Clinical and experimental studies unambiguously link misalignment of the body clock to cardiovascular disease, albeit through unknown mechanisms.