The main aim of our research is to study the molecular mechanisms underlying cardiac dysfunction in disease, particularly myocardial ischemia and the development of cardiac hypertrophy and failure. We employ physiological, biochemical and molecular approaches to develop and evaluate novel interventions for the inhibition and/or reversal of such dysfunction. Current research projects are focused on the regulation of kinase cascades (MAPKs, MSK1, PI-3-K/Akt) and transcription factors and their role in gene expression, the mechanisms underlying cytoprotective adaptation of cardiac myocytes to ischemia (preconditioning), the mechanisms regulating cardiac myocyte death, and the role of PPARs (peroxisome proliferator-activated receptors) in myocardial ischemia and hypertrophy.


1. The role of PPARs in myocardial resistance to ischemia/reperfusion. Involvement of signalling pathways in the regulation of PPAR transcriptional activity

Myocardial infarction (MI) and sudden death represents one of the main causes of mortality due to cardiovascular diseases. The primary cause of acute myocyte death is the oxidative stress generated during both the ischemic phase of MI and any subsequent adaptive reperfusion of the heart. Various other pathological conditions eg diabetes mellitus and NO-deficient hypertension are also associated with increased production of reactive oxygen species and have been implicated in the mechanisms of cell injury. Myocardial resistance to ischemic injury can be increased by way of activation of intrinsic protective mechanisms in the heart in response to various forms of stress and the signalling pathways which mediate this protective effect are under investigation. The aim of this project is to determine the role of peroxisome proliferator-activated receptor (PPAR) isoforms in the mechanisms of ischemia/ reperfusion injury and short-term adaptation of the heart to ischemia. Expression of PPARs (mRNA and protein levels) in the heart during ischemia/reperfusion as well as their phosphorylation in the intact and pathologically altered myocardium is determined. In addition, the kinases responsible for the phosphorylation of PPARs and the intracellular signalling pathways that contribute to adaptive processes will be identified in order to elucidate their role in the cardioprotective mechanism.

2. Regulatory mechanisms in cardiac myocyte cell death pathways (apoptosis, autophagy, necroptosis)

3. Cardioprotective effects of natural products and underlying mechanisms