CARDREG · Calcineurin isoforms in cardiac disease and regeneration
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-10-18 → 2008-10-17
- EU contribution
- €219,574
- Participants
- 1
- Scheme
- EIF
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Results in brief
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.
Data: CORDIS, © European Union
Project objective
Heart failure is one of the leading causes of human death. The limited capacity for cardiac self-repair after muscle cell death is one of the elemental challenges in human heart disease. Calcineurin (Cn) is a calcium-regulated Serine/Threonine phosphatase involved in a wide variety of biological processes, including heart development, neuronal plasticity and lymphocyte activation.We have recently demonstrated that expression of a naturally occurring splicing variant of the Cn catalytic subunit (termed CnAb eta1) is able to enhance skeletal muscle regeneration, reducing scar formation and inflammation.We hypothesize that CnAbeta1 expression in adult heart results in enhanced cardiac healing capacity and propose the following research aims:- To analyse of t he expression of the different CnA isoforms in human and mouse models of cardiac failure and regeneration- To analyse of the effect of expressing CnAbeta1 and its alternative splicing variant CnAbeta2 in the heart- To study the capacity of CnAbeta1 to enhance cardiac regeneration- To identify the signalling mechanisms triggered by CnAbeta1 Myocardial over-expression of CnAbeta1 and CnAbeta2 will be examined using a cardiac-specific transgenic mouse model and by cell-based delivery methods.Effects of C nAbeta1 on cardiac regeneration will be analysed in myocardial infarction and generalised heart failure models. The results obtained will provide key information for our understanding of the mechanisms underlying cardiac regeneration and calcineurin regulation and function, increasing the European knowledge base.Moreover, the proposed project will evaluate the potential of CnAbeta1 as a therapeutic agent for the treatment of heart failure, allowing the generation of new clinical protocols and drugs based o n the use of this molecule and thereby contributing to increase European competitiveness.
Original text from CORDIS.
Participants
- IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE · LONDONCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union