Head – Rebecca Ritchie
Scientist Rebecca Ritchie heads the Heart Failure Pharmacology lab, pursuing three main areas of research: the cellular mechanisms responsible for cardiac hypertrophy, or heart growth associated with disease; heart complications related to diabetes, and addressing reperfusion injury, the damage caused to the heart after a heart attack.
Work is building on their discovery that elevated levels of a small heart cell chemical called cyclic GMP, a natriuretic peptide, will prevent abnormal heart growth. They also have evidence that other such hormones also increase in response to this heart growth or cardiac hypertrophy, and work to stop it from worsening orprogressing to heart failure.
Rebecca’s work in cardiac hypertrophy has focused on identifying elements within the heart muscle cells themselves that might prevent this unwanted growth. Her most recent research showed that a different chemical form of nitric oxide, gas released by the innermost layer of the blood vessel wall, prevents hypertrophy by elevating levels of the cyclic GMP chemical within the cells. Continuing research will look at whether this gas has other effects not related to cyclic GMP which nonetheless protects against heart failure. It is well known that one of the contributing factors to hypertrophy and heart failure is oxidative stress, where the metabolic balance of a cell is disrupted and there is an increase in the body of harmful free radicals. The powerful antioxidant action of this gas, occurring naturally where there is injury to the heart, will be the focus of further study and has implications for the development of drugs that promote the production and release of these natriureticpeptide hormones.
The damage to the heart caused by diabetes is often characterised by hypertrophy, myocardial fibrosis (stiffening) and impaired pumping. Furthermore, diabetics with heart complications fare worse than non-diabetics with comparable cardiovascular disease. Work conducted in this lab suggests that free radicals play an important role and their presence has implications for the most appropriate way to treat heart disease specifically in diabetes. The changes in structure and function occurring in the hearts of rats with diabetes have been characterised and their research has shown that both the levels of free radicals and the enzymes that generate them are increased in rats and mice with both type 1 and type 2 diabetes. Studies are now focusing on whether boosting the genes thought to reduce the production and numbers of free radicals in the body will improve the health ofdiabetics with these complications.
Reperfusion injury can occur after a heart attack. Reduced blood supply to the heart, known as myocardial ischaemia, can lead to heart attack during which cells can die. But the damage does not always stop with a return of blood flow: in fact the death of cells can create its own havoc, releasing their own“nasties”, and restoring bloodflow – reperfusion – can causeadditional damage.
Rebecca’s hypothesis is that a naturally occurring, antiinflammatory protein called annexin-1 improves how the heart recovers from a heart attack. She believes that it may reduce the accumulation of inflammatory white blood cells and also maintain the viability and pumping action of the heart muscle following the event. Her research involves administering annexin-1 to mice and rats in which heart attack has been induced. Mouse models lacking annexin-1 are also studied for comparison, and in an effort to isolate its function. Understanding the protective role played by annexin-1 opens exciting new possibilities for reducing long-term damage from human heart attack.