PMID- 31704554
OWN - NLM
STAT- MEDLINE
DCOM- 20200803
LR  - 20200803
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 291
DP  - 2019 Dec
TI  - MicroRNA-21 deficiency attenuated atherogenesis and decreased macrophage 
      infiltration by targeting Dusp-8.
PG  - 78-86
LID - S0021-9150(19)31520-5 [pii]
LID - 10.1016/j.atherosclerosis.2019.10.003 [doi]
AB  - BACKGROUND AND AIMS: Atherosclerosis is a chronic inflammatory disorder mediated 
      by macrophage activation. MicroRNA-21 (miR-21) is a key regulator in the 
      macrophage inflammatory response. However, the functional role of miR-21 in 
      atherogenesis is far from clear. METHODS AND RESULTS: Here, we report that miR-21 
      is significantly upregulated in mouse atherosclerotic plaques and peripheral 
      monocytes from patients with coronary artery disease. Compared with 
      miR-21(+/+)apoE(-/-) mice (apoE(-/-) mice), miR-21(-/-)apoE(-/-) (double 
      knockout, DKO) mice showed less atherosclerotic lesions, reduced presence of 
      macrophages, decreased smooth muscle cells(SMC) and collagen content in the 
      aorta. We further explored the role of miR-21 in macrophage activation in vitro. 
      Bone marrow-derived macrophages (BMDMs) from DKO mice not only exhibit impaired 
      function of migration induced by chemokine (C-C motif) ligand 2 (CCL2) but also a 
      weakened macrophage-endothelium interaction activated by tumor necrosis factor-alpha 
      (TNF-alpha). However, atherogenic inflammatory cytokine secretion was not affected by 
      miR-21 in vitro or in vivo. Additionally, miR-21 knockdown in BMDMs directly 
      derepressed the expression of dual specificity protein phosphatase 8 (Dusp-8), a 
      previously validated miR-21 target in cardiac fibroblasts, which negatively 
      regulates mitogen-activated protein kinase (MAPK) signaling, particularly the 
      p38-and c-Jun N-terminal kinase (JNK)-related signaling pathways. CONCLUSIONS: 
      These data demonstrate that inhibition of miR-21 may restrict the formation of 
      atherosclerotic plaques partly by regulating macrophage migration and adhesion, 
      while, reduced SMCs and collagen content in plaques may lead to a less stable 
      phenotype with the progression of atherosclerosis. Thus, the absence of miR-21 
      reduces atherosclerotic lesions but may not represent all benefit in 
      atherosclerosis development.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Gao, Lin
AU  - Gao L
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Zeng, Huasu
AU  - Zeng H
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Zhang, Tiantian
AU  - Zhang T
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Mao, Chengyu
AU  - Mao C
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Han, Zhihua
AU  - Han Z
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Chen, Kan
AU  - Chen K
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Zhang, Junfeng
AU  - Zhang J
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China.
FAU - Fan, Yuqi
AU  - Fan Y
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China. 
      Electronic address: FANYQ1770@2m9h.net.
FAU - Gu, Jun
AU  - Gu J
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China. 
      Electronic address: 115009@2m9h.net.
FAU - Wang, Changqian
AU  - Wang C
AD  - Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai JiaoTong 
      University School of Medicine, Shanghai, 639 Zhizaoju Road, 200011, China. 
      Electronic address: wcqian@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191011
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MIRN21 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (DUSP8 protein, mouse)
RN  - EC 3.1.3.48 (Dual-Specificity Phosphatases)
SB  - IM
MH  - Animals
MH  - Aorta/*enzymology/pathology
MH  - Aortic Diseases/enzymology/genetics/pathology/*prevention & control
MH  - Atherosclerosis/enzymology/genetics/pathology/*prevention & control
MH  - Cell Adhesion
MH  - *Chemotaxis
MH  - Disease Models, Animal
MH  - Dual-Specificity Phosphatases/genetics/*metabolism
MH  - Endothelial Cells/metabolism/pathology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - *Macrophage Activation
MH  - Macrophages/*enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout, ApoE
MH  - MicroRNAs/genetics/*metabolism
MH  - Plaque, Atherosclerotic
MH  - RAW 264.7 Cells
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Adhesion
OT  - Atherosclerosis
OT  - Dual specificity protein phosphatase 8
OT  - Macrophage
OT  - Migration
OT  - microRNA-21
EDAT- 2019/11/11 06:00
MHDA- 2020/08/04 06:00
CRDT- 2019/11/10 06:00
PHST- 2018/12/10 00:00 [received]
PHST- 2019/09/10 00:00 [revised]
PHST- 2019/10/09 00:00 [accepted]
PHST- 2019/11/11 06:00 [pubmed]
PHST- 2020/08/04 06:00 [medline]
PHST- 2019/11/10 06:00 [entrez]
AID - S0021-9150(19)31520-5 [pii]
AID - 10.1016/j.atherosclerosis.2019.10.003 [doi]
PST - ppublish
SO  - Atherosclerosis. 2019 Dec;291:78-86. doi: 10.1016/j.atherosclerosis.2019.10.003. 
      Epub 2019 Oct 11.