PMID- 33637522
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240331
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 7
IP  - 9
DP  - 2021 Feb
TI  - Microglia control small vessel calcification via TREM2.
LID - 10.1126/sciadv.abc4898 [doi]
LID - eabc4898
AB  - 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.
CI  - Copyright (c) 2021 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 
      (CC BY-NC).
FAU - Zarb, Yvette
AU  - Zarb Y
AUID- ORCID: 0000-0001-5107-0701
AD  - Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, 
      Zurich University, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
FAU - Sridhar, Sucheta
AU  - Sridhar S
AUID- ORCID: 0000-0003-2699-0367
AD  - Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, 
      Zurich University, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
FAU - Nassiri, Sina
AU  - Nassiri S
AD  - Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, 
      Switzerland.
FAU - Utz, Sebastian Guido
AU  - Utz SG
AUID- ORCID: 0000-0001-5491-0219
AD  - Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
FAU - Schaffenrath, Johanna
AU  - Schaffenrath J
AUID- ORCID: 0000-0003-1689-1648
AD  - Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, 
      Zurich University, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
FAU - Maheshwari, Upasana
AU  - Maheshwari U
AUID- ORCID: 0000-0001-7516-3099
AD  - Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, 
      Zurich University, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
FAU - Rushing, Elisabeth J
AU  - Rushing EJ
AUID- ORCID: 0000-0001-7616-6320
AD  - Institute of Neuropathology, Zurich University Hospital, Zurich, Switzerland.
FAU - Nilsson, K Peter R
AU  - Nilsson KPR
AUID- ORCID: 0000-0002-5582-140X
AD  - Department of Chemistry, Linkoping University, Linkoping, Sweden.
FAU - Delorenzi, Mauro
AU  - Delorenzi M
AUID- ORCID: 0000-0001-7631-3263
AD  - Bioinformatics Core Facility, Swiss Institute of Bioinformatics, Lausanne, 
      Switzerland.
AD  - Department of Oncology, University Lausanne, Lausanne, Switzerland.
FAU - Colonna, Marco
AU  - Colonna M
AUID- ORCID: 0000-0001-5222-4987
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, MO, USA.
FAU - Greter, Melanie
AU  - Greter M
AD  - Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
FAU - Keller, Annika
AU  - Keller A
AUID- ORCID: 0000-0003-1466-3633
AD  - Department of Neurosurgery, Clinical Neurocentre, Zurich University Hospital, 
      Zurich University, Zurich, Switzerland. annika.keller@usz.ch.
AD  - Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, 
      Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210226
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
PMC - PMC7909879
EDAT- 2021/02/28 06:00
MHDA- 2021/02/28 06:01
PMCR- 2021/02/26
CRDT- 2021/02/27 05:32
PHST- 2020/04/27 00:00 [received]
PHST- 2021/01/15 00:00 [accepted]
PHST- 2021/02/27 05:32 [entrez]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/02/28 06:01 [medline]
PHST- 2021/02/26 00:00 [pmc-release]
AID - 7/9/eabc4898 [pii]
AID - abc4898 [pii]
AID - 10.1126/sciadv.abc4898 [doi]
PST - epublish
SO  - Sci Adv. 2021 Feb 26;7(9):eabc4898. doi: 10.1126/sciadv.abc4898. Print 2021 Feb.