PMID- 35227297
OWN - NLM
STAT- MEDLINE
DCOM- 20220303
LR  - 20220318
IS  - 1868-7083 (Electronic)
IS  - 1868-7075 (Print)
IS  - 1868-7075 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Feb 28
TI  - Atheroprotective mechanism by which folic acid regulates monocyte subsets and 
      function through DNA methylation.
PG  - 32
LID - 10.1186/s13148-022-01248-0 [doi]
LID - 32
AB  - BACKGROUND: Recent studies have suggested that folic acid can restore abnormal 
      DNA methylation and monocyte subset shifts caused by hyperhomocysteinemia (HHcy) 
      and hyperlipidemia (HL). However, the exact mechanism of action is still not 
      fully understood. In this study, we further investigated the reversal effect and 
      underlying mechanism of folic acid on the shift in monocyte subsets induced by 
      aberrant lipids and Hcy metabolism via DNA methylation in vitro and in vivo. 
      RESULTS: Our results showed that intermediate monocytes were significantly 
      increased but had the lowest global 5-methylcytosine (5-mC) levels in coronary 
      artery disease (CAD) patients, which might lead to a decrease in the global 5-mC 
      levels of peripheral blood leukocytes (PBLs). We also discovered that ARID5B 
      might mediate the increased proportion of intermediate monocytes, as this factor 
      was related to the proportion of monocyte subsets and the expression of CCR2. The 
      expression of ARID5B was inversely associated with the hypermethylated cg25953130 
      CpG site, which was induced by HL and HHcy. ARID5B could also regulate monocyte 
      CCR2, MCP-1, and TNF-alpha expression, adhesion and migration, macrophage 
      polarization, and monocyte/macrophage apoptosis, which might explain the 
      regulatory effect of ARID5B on monocyte subset shifting. Folic acid reversed HL- 
      and HHcy-mediated aberrant global and cg25953130 DNA methylation, reduced the 
      proportion of intermediate monocytes, and inhibited the formation of 
      atherosclerotic plaques. CONCLUSION: Folic acid plays a protective role against 
      atherosclerosis through the regulation of DNA methylation, ARID5B expression, and 
      monocyte subsets.
CI  - (c) 2022. The Author(s).
FAU - Xiang, Yang
AU  - Xiang Y
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China.
FAU - Liang, Bin
AU  - Liang B
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China.
FAU - Zhang, Xiaokang
AU  - Zhang X
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China.
FAU - Qiu, Xueping
AU  - Qiu X
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China.
FAU - Deng, Qianyun
AU  - Deng Q
AD  - Laboratory Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of 
      Medical Sciences, Guangzhou, China.
FAU - Yu, Li
AU  - Yu L
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China.
FAU - Yu, Hong
AU  - Yu H
AD  - Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 
      University School of Basic Medical Sciences, Wuhan, 430071, Hubei, China.
FAU - Lu, Zhibing
AU  - Lu Z
AD  - Institute of Myocardial Injury and Repair, Zhongnan Hospital of Wuhan University, 
      Donghu Road 169, Wuhan, 430071, China.
FAU - Zheng, Fang
AU  - Zheng F
AUID- ORCID: 0000-0002-2024-2424
AD  - Center for Gene Diagnosis, and Department of Clinical Laboratory Medicine, 
      Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, China. 
      zhengfang@whu.edu.cn.
LA  - eng
GR  - 81871722/National Natural Science Foundation of China/
GR  - 82072373/National Natural Science Foundation of China/
GR  - 82002235/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220228
PL  - Germany
TA  - Clin Epigenetics
JT  - Clinical epigenetics
JID - 101516977
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - *Atherosclerosis/genetics/metabolism
MH  - DNA Methylation
MH  - Folic Acid/metabolism/pharmacology
MH  - Humans
MH  - Monocytes/metabolism
MH  - *Plaque, Atherosclerotic/genetics
PMC - PMC8887029
OTO - NOTNLM
OT  - ARID5B
OT  - Coronary artery disease
OT  - DNA methylation
OT  - Folic acid
OT  - Monocyte subsets
COIS- The authors declare that they have no competing interests.
EDAT- 2022/03/02 06:00
MHDA- 2022/03/04 06:00
PMCR- 2022/02/28
CRDT- 2022/03/01 05:42
PHST- 2021/10/26 00:00 [received]
PHST- 2022/02/14 00:00 [accepted]
PHST- 2022/03/01 05:42 [entrez]
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/03/04 06:00 [medline]
PHST- 2022/02/28 00:00 [pmc-release]
AID - 10.1186/s13148-022-01248-0 [pii]
AID - 1248 [pii]
AID - 10.1186/s13148-022-01248-0 [doi]
PST - epublish
SO  - Clin Epigenetics. 2022 Feb 28;14(1):32. doi: 10.1186/s13148-022-01248-0.