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Athero MPh proliferation

Macrophage proliferation and ontogeny in murine models of atherosclerosis

Total Cost €

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EC-Contrib. €

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Partnership

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 Athero MPh proliferation project word cloud

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Project "Athero MPh proliferation" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT MAASTRICHT 

Organization address
address: Minderbroedersberg 4-6
city: MAASTRICHT
postcode: 6200 MD
website: http://www.maastrichtuniversity.nl

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 Netherlands [NL]
 Project website https://pathologie.mumc.nl/nl/medewerkers/goossens
 Total cost 177˙598 €
 EC max contribution 177˙598 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-02-01   to  2018-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITEIT MAASTRICHT NL (MAASTRICHT) coordinator 177˙598.00

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 Project objective

Atherosclerosis is a slowly progressing inflammatory disease that underlies some of the most common causes of death in western society. The central role of macrophages throughout its pathogenesis makes this cell an eminent target for therapeutic intervention. Recent studies have subverted the classical view that atherosclerotic plaque macrophages mainly originate from recruited circulating monocytes, launching the new notion that macrophages could also be derived from clonal expansion of resident macrophages or even trans-differentiated vascular smooth muscle cells. The relative importance of these mechanisms to the pathogenesis remains however unclear, due to a lack of adequate animal models that allow assessing this question. In this project, I introduce a recently developed fate mapping model, the LysMCre-Ubow/ mouse, into the atherosclerosis field to conclusively identify regions within the plaque that were formed through local proliferation rather than monocyte recruitment. Apart from quantifying its relative contribution to plaque growth during disease progression and regression, I will furthermore characterize the localization, transcriptional activity and the lipidic makeup of these proliferated cells versus invaded monocytes. In a second part of this project, I will deploy adoptive bone marrow transfers from WT to Ubow mice and vice versa as a model to quantify intraplaque myeloid versus stromal-cell derived macrophages. I will compare proliferative capacity, phenotype, transcriptomics and lipidomics of these two subsets and link this information to their functionality. With this strategy I will be the first to reveal the impact of the three macrophage accumulation mechanisms throughout the disease course, to couple this to their function and to exploit this knowledge for targeted experimental therapeutic interventions.

 Publications

year authors and title journal last update
List of publications.
2017 Emiel P.C. van der Vorst, Kosta Theodorou, Yongzheng Wu, Marten A. Hoeksema, Pieter Goossens, Christina A. Bursill, Taghi Aliyev, Leonie F.A. Huitema, Sander W. Tas, Ine M.J. Wolfs, Marijke J.E. Kuijpers, Marion J. Gijbels, Casper G. Schalkwijk, Debby P.Y. Koonen, Shahla Abdollahi-Roodsaz, Kimberly McDaniels, Chih-Chieh Wang, Michael Leitges, Toby Lawrence, Jogchum Plat, Miranda Van Eck, Kerry-Anne Rye, Lhousseine Touqui, Menno P.J. de Winther, Erik A.L. Biessen, Marjo M.P.C. Donners
High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-κB/STAT1-IRF1 Signaling
published pages: 197-207, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2016.10.013
Cell Metabolism 25/1 2019-06-18
2017 Jan Nagenborg, Pieter Goossens, Erik A.L. Biessen, Marjo M.P.C. Donners
Heterogeneity of atherosclerotic plaque macrophage origin, phenotype and functions: Implications for treatment
published pages: 14-24, ISSN: 0014-2999, DOI: 10.1016/j.ejphar.2017.10.005
European Journal of Pharmacology 816 2019-06-18

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