Community Research and Development Information Service - CORDIS


CARDIONECT Report Summary

Project ID: 323099
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - CARDIONECT (Cardiac Connective Tissue: Beat-by-Beat Relevance for Heart Function in Health and Disease)

Like any other complex organ, the heart consists of different interacting cell populations. Prior fundamental and applied heart research has been focussed mainly at muscle cells, whose coordinated electrical activation gives rise to well-synchronised mechanical contraction, which underlies the pump function of the heart. Interestingly, while these myocytes occupy the largest part of the cardiac tissue volume, other (smaller) cells are more numerous. Among these majority cell populations, connective tissue cells are of particular interest, as they provide the deformable extra-cellular matrix ‘skeleton’ of the heart. Beyond the making and sustenance of this meshwork, connective tissue cells are known to fulfil a number of biochemical signalling functions and, under certain conditions, they are thought to possibly be able to transform into heart muscle-like cells. What is less well known is that fibroblasts also serve as *biophysical_signalling* hubs in the heart, with important mechanical and electrical roles for normal and disturbed heart function. These include electrical insulation of regions of heart muscle that benefit from sequential activation and, perhaps counter-intuitively, the potential for electrical connection with / between muscle cells. This has been experimentally confirmed in native heart tissue during the first 2.5 years of the present ERC investigation, and this knowledge is now being rolled out to a large-scale investigation that (i) explores fibroblast sub-types (they are a heterogeneous cell population in their own right), (ii) assesses distribution of fibroblast-myocyte electrical coupling in different parts of the normal and the diseased hearts (focussing in particular on cardiac scar tissue, such as formed upon myocardial infarction or during catheter ablation to cure pre-existing heart rhythm disturbances), (iii) establishes the molecular substrates of coupling (we have discovered ‘tunnelling nanotubes’ between fibroblasts and myocytes in cardiac scar border tissue that are likely to be of relevance, in addition to more classically known connexin-protein channels between different cell types), and (iv) translates this insight towards exploring how one may modulate fibroblast electrical activity and coupling to myocytes for patient benefit.

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