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Targeting epigenetic REPROGRamming of innate immune cells in Atherosclerosis Management and other chronic inflammatory diseases

Targeting epigenetic REPROGRamming of innate immune cells in Atherosclerosis Management and other chronic inflammatory diseases

Objective

Up to 70% of cardiovascular events are not prevented by current therapeutic regimens. In search for additional, innovative strategies, immune cells have been recognized as key players contributing to atherosclerotic plaque progression and destabilization. Particularly the role of innate immune cells is of major interest, following the recent paradigm shift that innate immunity, considered to be incapable of learning ability, does exhibit a memory feature transduced via epigenetic modulation. Compelling evidence shows that atherosclerotic factors promote immune cell migration by pre-activation of innate immune cells. In this project called REPROGRAM, we aim to prove that innate immune cell activation via epigenetic reprogramming perpetuates the upheld systemic inflammatory state in cardiovascular disease which is common in other chronic inflammatory diseases. This opens a new therapeutic area in which epigenetic modulation of innate immune cells effectively decreases systemic inflammation impacting on chronic inflammation as well as the development of co-morbidities. The integrated use of in vitro, ex vivo and in vivo studies, including cells, mice and patients, allows translation from in vitro mechanisms to diseases (molecule-to-man) and extrapolation to cohorts (man-to-mass), enabling us to demonstrate relevance and therapeutic potential of targeting trained immunity in cardiovascular and chronic inflammatory diseases. Enforced by the promising data in oncology, the future prospects for epigenetic interventions in cardiovascular and chronic inflammatory diseases are eminent, attested by the large residual cardiovascular disease burden and the huge societal impact of other chronic inflammatory diseases. The REPROGRAM consortium consisting of key opinion leaders in the field of cardiovascular (systems) biology, immunology, epigenetic therapies and rheumatoid arthritis, with a large intersectoral network, guarantees rapid translation of early mechanistic discoveries

Coordinator

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Address

Meibergdreef 9
1105az Amsterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 112 625

Participants (10)

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STICHTING KATHOLIEKE UNIVERSITEIT

Netherlands

EU Contribution

€ 973 500

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

Germany

EU Contribution

€ 925 000

REGION HOVEDSTADEN

Denmark

EU Contribution

€ 255 000

UNIVERSITATEA DE MEDICINA SI FARMACIE IULIU HATIEGANU CLUJ-NAPOCA

Romania

EU Contribution

€ 232 500

UNIVERSITA DEGLI STUDI DI MILANO

Italy

EU Contribution

€ 587 375

UNIVERSITAT ZURICH

Switzerland

THE GENERAL HOSPITAL CORPORATION

United States

EU Contribution

€ 600 000

SENSILAB POLSKA SP ZOO - SKA

Poland

EU Contribution

€ 117 500

INSTITUT DE RECHERCHES INTERNATIONALES SERVIER

France

EU Contribution

€ 225 000

DESCIN BV

Netherlands

EU Contribution

€ 221 500

Project information

Grant agreement ID: 667837

Status

Ongoing project

  • Start date

    1 January 2016

  • End date

    31 December 2019

Funded under:

H2020-EU.3.1.1.

  • Overall budget:

    € 6 000 000

  • EU contribution

    € 5 250 000

Coordinated by:

Academisch Medisch Centrum bij de Universiteit van Amsterdam

Netherlands