PMID- 35835907
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20220922
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jul 14
TI  - Loss of PRMT2 in myeloid cells in normoglycemic mice phenocopies impaired 
      regression of atherosclerosis in diabetic mice.
PG  - 12031
LID - 10.1038/s41598-022-15349-6 [doi]
LID - 12031
AB  - The regression, or resolution, of inflammation in atherosclerotic plaques is 
      impaired in diabetes. However, the factors mediating this effect remain 
      incomplete. We identified protein arginine methyltransferase 2 (PRMT2) as a 
      protein whose expression in macrophages is reduced in hyperglycemia and diabetes. 
      PRMT2 catalyzes arginine methylation to target proteins to modulate gene 
      expression. Because PRMT2 expression is reduced in cells in hyperglycemia, we 
      wanted to determine whether PRMT2 plays a causal role in the impairment of 
      atherosclerosis regression in diabetes. We, therefore, examined the consequence 
      of deleting PRMT2 in myeloid cells during the regression of atherosclerosis in 
      normal and diabetic mice. Remarkably, we found significant impairment of 
      atherosclerosis regression under normoglycemic conditions in mice lacking PRMT2 
      (Prmt2(-/-)) in myeloid cells that mimic the decrease in regression of 
      atherosclerosis in WT mice under diabetic conditions. This was associated with 
      increased plaque macrophage retention, as well as increased apoptosis and 
      necrosis. PRMT2-deficient plaque CD68+ cells under normoglycemic conditions 
      showed increased expression of genes involved in cytokine signaling and 
      inflammation compared to WT cells. Consistently, Prmt2(-/-) bone marrow-derived 
      macrophages (BMDMs) showed an increased response of proinflammatory genes to LPS 
      and a decreased response of inflammation resolving genes to IL-4. This increased 
      response to LPS in Prmt2(-/-) BMDMs occurs via enhanced NF-kappa B activity. 
      Thus, the loss of PRMT2 is causally linked to impaired atherosclerosis regression 
      via a heightened inflammatory response in macrophages. That PRMT2 expression was 
      lower in myeloid cells in plaques from human subjects with diabetes supports the 
      relevance of our findings to human atherosclerosis.
CI  - (c) 2022. The Author(s).
FAU - Vurusaner, Beyza
AU  - Vurusaner B
AD  - Division of Cardiology, Department of Medicine, Cardiovascular Research Center, 
      New York University Grossman School of Medicine, 435 E. 30th Street, Room 705, 
      New York, NY, 10016, USA.
FAU - Thevkar-Nages, Prashanth
AU  - Thevkar-Nages P
AD  - Division of Cardiology, Department of Medicine, Cardiovascular Research Center, 
      New York University Grossman School of Medicine, 435 E. 30th Street, Room 705, 
      New York, NY, 10016, USA.
AD  - Department of Microbiology, New York University Grossman School of Medicine, 450 
      E. 29th Street, Room 321, New York, NY, 10016, USA.
FAU - Kaur, Ravneet
AU  - Kaur R
AD  - Division of Cardiology, Department of Medicine, Cardiovascular Research Center, 
      New York University Grossman School of Medicine, 435 E. 30th Street, Room 705, 
      New York, NY, 10016, USA.
FAU - Giannarelli, Chiara
AU  - Giannarelli C
AD  - Division of Cardiology, Department of Medicine, Cardiovascular Research Center, 
      New York University Grossman School of Medicine, 435 E. 30th Street, Room 705, 
      New York, NY, 10016, USA.
FAU - Garabedian, Michael J
AU  - Garabedian MJ
AD  - Department of Microbiology, New York University Grossman School of Medicine, 450 
      E. 29th Street, Room 321, New York, NY, 10016, USA. 
      michael.garabedian@nyulangone.org.
FAU - Fisher, Edward A
AU  - Fisher EA
AD  - Division of Cardiology, Department of Medicine, Cardiovascular Research Center, 
      New York University Grossman School of Medicine, 435 E. 30th Street, Room 705, 
      New York, NY, 10016, USA. Edward.Fisher@nyulangone.org.
AD  - Department of Microbiology, New York University Grossman School of Medicine, 450 
      E. 29th Street, Room 321, New York, NY, 10016, USA. Edward.Fisher@nyulangone.org.
AD  - Marc and Ruti Bell Vascular Biology Program, New York University Grossman School 
      of Medicine, New York, NY, 10016, USA. Edward.Fisher@nyulangone.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20220714
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.1.1.319 (PRMT2 protein, human)
RN  - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
SB  - IM
MH  - Animals
MH  - *Atherosclerosis/metabolism
MH  - *Diabetes Mellitus, Experimental/complications/genetics
MH  - Humans
MH  - *Hyperglycemia/complications
MH  - Inflammation/complications/genetics
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lipopolysaccharides
MH  - Mice
MH  - Myeloid Cells/metabolism
MH  - *Plaque, Atherosclerotic/complications/genetics
MH  - Protein-Arginine N-Methyltransferases/genetics
PMC - PMC9283439
COIS- The authors declare no competing interests.
EDAT- 2022/07/15 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/07/14
CRDT- 2022/07/14 23:27
PHST- 2022/04/08 00:00 [received]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/07/14 23:27 [entrez]
PHST- 2022/07/15 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/07/14 00:00 [pmc-release]
AID - 10.1038/s41598-022-15349-6 [pii]
AID - 15349 [pii]
AID - 10.1038/s41598-022-15349-6 [doi]
PST - epublish
SO  - Sci Rep. 2022 Jul 14;12(1):12031. doi: 10.1038/s41598-022-15349-6.