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Calcineurin isoforms in cardiac disease and regeneration

Final Activity Report Summary - CARDREG (Calcineurin isoforms in cardiac disease and regeneration)

Heart failure remains one of the leading causes of morbidity and mortality. As the adult myocardium has insufficient regenerative capacity cardiac myocyte loss as a result of injury or disease is essentially irreversible. Therefore, individuals who suffer large acute myocardial infarction (heart attack) or dilated/hypertrophic cardiomyoyopathy often progress to heart failure. Despite significant advances in medical management, the prognosis of end-stage congestive heart failure remains very poor and the identification of mechanisms and potential therapeutic approaches for the treatment of heart failure remains of considerable importance.

In this project we have identified a particular molecule, called CnAbeta1, with strong regenerative properties. CnAbeta1 is naturally expressed in stem/progenitor cells and developing tissues. We have shown that increasing the expression of CnAbeta1 in skeletal muscle enhances its regeneration capacity, resolving inflammation faster and reducing the formation of a scar. In the heart, increased expression of CnAbeta1 prevents cardiac atrophy and, more importantly, it induces cardiac recovery after myocardial infarction. CnAbeta1 reduces inflammation and the formation of a scar and promotes the appearance of new cardiac myocytes, which contributes to the improvement in heart performance.