MRC PhD students

MRC Career award, new recipient

Project: Delineation and characterisation of new protective mechanisms leading to cardioprotection.

A recent World Health Organization report warns of the escalating global burden of cardiovascular diseases (CVD), projecting that it will become the major worldwide cause of death and disability by 2020. The perception that CVD is not relevant to developing countries is wrong. In fact, these countries are undergoing a more rapid increase in prevalence of CVD than the developed countries. In the Western Cape region of South Africa, ischaemic heart disease is already the leading cause of death, often killing by a heart attack. The blood-deprived ischaemic cells take about 3-4 hrs to die (myocardial infarction, MI). The best hope of salvaging threatened viable myocardium is by rapid reperfusion of the ischaemic myocardium, especially by primary percutaneous coronary intervention. However, despite such effective reperfusion strategies, about one third of the reperfused cells will die during the reperfusion period, so that additional strategies are required. Recently, the discovery of ischemic preconditioning and postconditioning has brought new hope. In each case, protection is achieved by repeated brief bouts of ischaemia either before or after the potentially lethal ischaemia respectively. Of these, ischaemic postconditioning is the more practical as it can be applied at the time of reperfusion therapy when the patient is in a coronary care unit in hospital. However, the long term beneficial effect has not been studied yet and the mechanisms that underlie this phenomenon remain to be elucidated.

We have recently identified the crucial role of the immune system in cardioprotection with the cytokine Tumor Necrosis Factor alpha (TNFα) and the nuclear regulatory peptide Signal Transducer and Activator of Transcription-3 (STAT-3) as playing a critical role in ischaemic preconditioning. Our research aims to delineate and characterize the role of both TNFα and STAT-3 in ischaemic pre- and postconditioning.