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REstoring myocardial repair capacity via the modulation of MAcrophage-mediated cytoKINe secretion.

Project description

Improving the recovery of type 2 diabetes patients after myocardial infarctions

Type 2 diabetes (T2D) is a chronic condition strongly associated with cardiovascular diseases, including recurrent myocardial infarctions (MI). The recovery of the heart after MI involves macrophages and efferocytosis-mediated cytokine secretion, promoting vessel formation and tissue reperfusion and decreasing inflammation via the anti-inflammatory cytokines interleukin-10 and vascular endothelial growth factor-A. The efferocytosis-mediated cytokine secretion process is impaired in T2D patients. The EU-funded REMAKIN project will investigate the mechanisms of this process and work on restoring cytokine secretion in T2D macrophages as a novel cell-based therapeutic strategy for improving the recovery of T2D patients after MI and preventing the recurrence of cardiac events.

Objective

Type-2 diabetes (T2D) is a chronic condition strongly associated with cardiovascular diseases, mainly recurrent myocardial infarctions (MI), and generating enormous healthcare cost. Macrophages orchestrate the remodelling of the heart post-MI by efferocytosis-mediated cytokine secretion. Specifically, Mertk-mediated efferocytosis promotes vessel formation, tissue reperfusion and resolution of the inflammatory response via the secretion of the anti-inflammatory cytokines interleukin-10 (IL-10) and Vascular Endothelial Growth Factor-A (VEGF-A). In IR/T2D, efferocytosis-mediated cytokine secretion is impaired, leading to chronic inflammation, adverse post-MI remodelling, recurrent heart failure and excessive mortality. To date, the signalling and intracellular trafficking pathways leading to cytokines secretion are unknown, and the mechanisms of impairment during IR/T2D are unexplored. Previous therapeutic strategies focussed on repairing damaged tissue by injection of progenitor cells or modulating inflammation by cytokine injection, but both strategies gave disappointing results. In this proposal, I will define the mechanisms of efferocytosis-mediated cytokine secretion in macrophages, investigate their defects in IR/T2D and test a novel cell-based therapeutic strategy for improving recovery of T2D patients post-MI and preventing recurrence of cardiac events by restoring cytokine secretion in diabetic macrophages.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-ST - Standard EF

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 196 707,84
Address
RUE DE TOLBIAC 101
75654 Paris
France
Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 196 707,84