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Assoc. Prof. Joost Sluijter,
View the Slides from this session in ESC Congress 365
The morbidity and mortality from ischemic heart disease (IHD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past few decades, including early reperfusion of occluded coronary arteries. Although it is essential to re-open the artery as soon as possible, paradoxically this leads to additional myocardial injury, called acute ischemia-reperfusion injury (IRI), for which currently no effective therapy is available. Therefore, novel therapeutic strategies are required to protect the heart from acute IRI in order to reduce myocardial infarction size, preserve cardiac function and improve clinical outcomes in patients with IHD.
In the first lecture, Dr. Jeremy Fauconnier (Montpellier, FR) highlighted the central role of reactive oxygen species that are produced within the myocardial cells and released by infiltrating inflammatory cells during ischemia. However, during the reperfusion phase an excessive amount of oxygen leads to the generation of more ROS and thereby increased myocardial damage. New strategies focussed on the interaction of the sarcoplasmic reticulum and mitochondria, opening of mitochondrial pores and leakage of calcium. Several levels of interventions were discussed that are focussed on influencing cellular death.
Subsequently, Dr Sean Davidson (London, GB) highlighted the beneficial effect of remote ischemic conditioning, via e.g. temporal occlusion of peripheral arteries, which lead to infarct reduction in the myocardium. The mechanism underlying this effect is not understood but should be mediated via neural or humoral factors. A new mediator is a population of small nano-sized vesicles (nanometre in size) that are released by several cell types upon stress signals. These vesicles are increasingly present in IRI animal models and patients due to ischemia and lead to a cardiac protective effect on the myocardium, via activating myocyte ERK signalling.
The IRI effects are a complex interplay of several pathways and mediators. Dr Zoltan Varga (Budapest, HU) highlighted the role of a new player in gene regulation called microRNAs (miRNAs). These miRNAs are small 18-22 base-pair long RNA molecules that are not translated into proteins but are involved in the post-transcriptional regulation of other RNA molecules. The current concept is that a set of miRNAs can regulate a whole cellular response, thereby targeting multiple levels in a signal cascade. Interventions are possible by the development of specific inhibitors for individual miRNAs. In the lecture several new miRNA candidates have been discovered that play a role in remote condition and promising infarct reduction effects are demonstrated when these where inhibited.
Finally, Dr Zoltan Moskaug (Oslo, NO) focused on the use of stem cell transplantation for cardioprotection. Many reports have shown a reduction in myocardial injury when stem cells are directly injected in the myocardium, probably mediated via the release of factors by the cells that target the ischemic myocytes. Here, a subcutaneous injection of cells was explored that released factors remotely and demonstrate promising effects on the ischemic myocardium. This would allow a less-invasive cell transplantation approach to help patients in the acute setting of a myocardial infarction.
In summary, cardioprotection strategies are still essential and needed although great effects have been achieved for patients by early reperfusion of occluded coronary arteries. Due to the complex nature of the response, translation of novel interventions has been hampered last years but promising pre-clinical effects are stimulating and motivating for future follow-ups.For more information on this topic please have a look at the position papers from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology (http://www.ncbi.nlm.nih.gov/pubmed/23334258 and http://www.ncbi.nlm.nih.gov/pubmed/24837132)
Novel therapeutic strategies for cardioprotection, Science in Practice on heart protection
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