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EXpansion and Phenotype Loss Of SMCs In Atherosclerosis: Causal effects and therapeutic possibilities

Total Cost €


EC-Contrib. €






 EXPLOSIA project word cloud

Explore the words cloud of the EXPLOSIA project. It provides you a very rough idea of what is the project "EXPLOSIA" about.

strikingly    expression    manipulating    forming    combining    smcs    hypothesise    development    central    prevent    human    first    subtypes    transcriptomics    mice    cellular    alter    heroes    undergoing    signature    genes    macrophages    tissue    dichotomous    entire    lipoproteins    tracking    plaques    causal    modulated    accumulation    expansion    conventional    wall    plaque    perturbing    thrombosis    massive    causing    carry    population    deeper    explosia    disease    phenotypic    lesion    architecture    immune    muscle    gene    atherosclerosis    humans    founder    completely    programs    balance    phenotype    functions    detection    modification    atherosclerotic    structure    uncovered    single    cell    minipigs    interventions    links    whereas    inflammatory    undergo    conduct    lose    answer    clonal    recognition    escaped    found    derives    dangerous    villains    arterial    caused    density    view    lineage    protective    modulation    cells    smc    rupture    questions    activity    progression    smooth    techniques    function    fibrous    modified    stabilises    hypothesis    few    drivers   

Project "EXPLOSIA" data sheet

The following table provides information about the project.


Organization address
city: AARHUS C
postcode: 8000

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Total cost 1˙998˙875 €
 EC max contribution 1˙998˙875 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-04-01   to  2025-03-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    AARHUS UNIVERSITET DK (AARHUS C) coordinator 1˙296˙120.00


 Project objective

Atherosclerosis is considered an inflammatory disease caused by the accumulation, modification and immune cell recognition of low-density lipoproteins in the arterial wall. Plaque macrophages are held to be the main drivers of disease activity, whereas smooth muscle cells (SMCs) have traditionally been considered protective by forming fibrous tissue that stabilises plaques from undergoing rupture and causing thrombosis. In the present project, we challenge this dichotomous view of cellular villains and heroes in atherosclerosis. Using lineage tracking techniques in mice, we and others have uncovered a large population of SMCs in plaques, which has escaped detection because the cells completely lose conventional SMC phenotype. Strikingly, we have found that the entire plaque SMC population derives from only few founder SMCs that undergo massive clonal expansion and phenotypic modulation during lesion formation. We hypothesise that the balance between the different modulated SMC subtypes and the functions they carry are central to lesion progression. In EXPLOSIA we will address this hypothesis in 3 steps. First, we will conduct a comparative analysis of clonal structure in mice, minipigs, and humans. Second, we will determine links between SMC subtypes, their gene expression programs, and atherosclerotic disease activity by combining single-cell transcriptomics with novel techniques to alter atherosclerotic disease activity in gene-modified mice and minipigs. Third, we will develop techniques for manipulating genes in modulated plaque SMCs and test the causal role of perturbing SMC subtypes and function for lesion progression.

The aim of the project is to answer the following key questions for a deeper understanding of atherosclerosis: - What is the clonal architecture of SMCs in human atherosclerosis? - What is the SMC gene expression signature of atherosclerotic disease activity? - Can interventions targeting SMCs prevent dangerous lesion development?

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The information about "EXPLOSIA" are provided by the European Opendata Portal: CORDIS opendata.

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