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Microglia control small vessel calcification via TREM2
Zurich Univ, Switzerland; Univ Zurich, Switzerland; Swiss Fed Inst Technol, Switzerland; Ludwig Maximilians Univ Munchen, Germany.
Zurich Univ, Switzerland; Univ Zurich, Switzerland; Swiss Fed Inst Technol, Switzerland.
Swiss Inst Bioinformat, Switzerland.
Univ Zurich, Switzerland.
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2021 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 9, article id eabc4898Article in journal (Refereed) Published
Abstract [en]

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfb(ret/ret), to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

Place, publisher, year, edition, pages
American Association for the Advancement of Science , 2021. Vol. 7, no 9, article id eabc4898
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-174139DOI: 10.1126/sciadv.abc4898ISI: 000622481300005PubMedID: 33637522OAI: oai:DiVA.org:liu-174139DiVA, id: diva2:1537237
Note

Funding Agencies|Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [31003A_159514, 310030_188952, PP00P3_170626, BSGI0_155832]; European Research Council under the European UnionEuropean Research Council (ERC) [819229]; Synapsis Foundation; Choupette Foundation [2019-PI02]; Fonds zur Forderung des akademischen Nachwuchses (Zurich University); Leducq FoundationLeducq Foundation [14CVD02]; Swiss Heart Foundation; Swiss Cancer League [KLS-3848-02-2016]; Forschungskredit und Stiftung fur Forschung an der Medizinischen Fakultat der Universitat Zurich [FK-16-034]

Available from: 2021-03-15 Created: 2021-03-15 Last updated: 2021-04-13

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