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Cardiac Connective Tissue Beat by Beat Relevance for Heart Function in Health a...

Cardiac Connective Tissue Beat by Beat Relevance for Heart Function in Health and Disease Cardiac connective tissue is regarded as passive in terms of cardiac electro-mechanics. However, recent evidence confirms that fibroblasts interact directly with cardiac muscle cells in a way that is likely to affect their beat-by... ver más

30/06/2019

UKLFR

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAETSKLINIKUM FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2019-06-30 No tenemos la información de la convocatoria

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2 Participantes

UKLFR

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IMPERIAL COLLEGE OF SCIENCE...

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Líder del proyecto

UNIVERSITAETSKLINIKUM FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cardiac connective tissue is regarded as passive in terms of cardiac electro-mechanics. However, recent evidence confirms that fibroblasts interact directly with cardiac muscle cells in a way that is likely to affect their beat-by-beat activity. To overcome limitations of traditional approaches to exploring these interactions in native tissue, we will build and explore murine models that express functional reporters (membrane potential, Vm; calcium concentration, [Ca2+]i) in fibroblasts, to identify how they are functionally integrated in native heart (myocyte => fibroblast effects). Next, we will express light-gated ion channels in murine fibroblast, to selectively interfere with their Vm (fibroblast => myocyte effects). Fibroblast-specific observation and interference will be conducted in normal and pathologically remodelled tissue, to characterise fibroblast relevance for heart function in health & disease. Based on these studies, we will generate 2 transgenic rabbits (fibroblast Vm reporting / interfering). Rabbit cardiac structure-function is more amenable to translational work, e.g. to study fibroblast involvement in normal origin & spread of excitation across the heart, in pathological settings such as arrhythmogenicity of post-infarct scars (a leading causes of sudden death), or as a determinant of therapeutic outcomes such as in healing of atrial ablation lines (interfering with a key interventions to treat atrial fibrillation). The final ‘blue-skies’ study will assess whether modulation of cardiac activity, from ‘tuning’ of biological pacemaker rates to ‘unpinning’ / termination of re-entrant excitation waves, can be achieved by targeting not myocytes, but fibroblasts. The study integrates basic-science-driven discovery research into mechanisms and dynamics of biophysical myocyte-fibroblast interactions, generation of novel transgenic models useful for a broad range of studies, and elucidation of conceptually new approaches to heart rhythm management.

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