PMID- 34750028
OWN - NLM
STAT- MEDLINE
DCOM- 20220301
LR  - 20220531
IS  - 1876-4738 (Electronic)
IS  - 0914-5087 (Linking)
VI  - 79
IP  - 3
DP  - 2022 Mar
TI  - Inhibition of MicroRNA-92 alleviates atherogenesis by regulation of macrophage 
      polarization through targeting KLF4.
PG  - 432-438
LID - S0914-5087(21)00289-6 [pii]
LID - 10.1016/j.jjcc.2021.10.015 [doi]
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory disease in which macrophage 
      polarization plays an important role in contribution to atherosclerotic plaque 
      formation and stability. Here we tested the effect of miR-92 regulation on the 
      development of atherosclerosis beyond tumorigenesis and explored the potential 
      mechanism. METHODS AND RESULTS: In the present study, bone marrow derived 
      macrophages (BMDMs), mouse peritoneal macrophages (MPMs), and human macrophages 
      were used to test the expression of miR-92. Here we noticed miR-92 levels were 
      enhanced in classic M1 macrophage but decreased in alternative M2 macrophage, 
      respectively. In vitro, we demonstrated that macrophages transfected with miR-92 
      inhibitor attenuated proinflammatory cytokine secretion represented by polarized 
      M1 markers but promoted anti-inflammatory state that was indicative of an M2 
      phenotype. Mechanistically, miR-92 was found to directly interact with KLF4 and 
      we further identified a requirement role of KLF4 in mediating the effect of 
      miR-92 silencing macrophage polarization. Concomitantly, miR-92 inhibition 
      treated ApoE(-/-) mice promoted macrophage polarization toward alternative M2 
      macrophage, thus protecting against atherosclerotic plaque formation and 
      preventing a vulnerable phenotype. CONCLUSION: miR-92 inhibition promoted 
      alternative macrophage activation and attenuated atherosclerosis regression 
      partially regulated in a KLF4-dependent manner, which indicated that miR-92/KLF4 
      axis may serve as a promising strategy for prevention of atherosclerotic 
      diseases.
CI  - Copyright (c) 2021. Published by Elsevier Ltd.
FAU - Gao, Feng
AU  - Gao F
AD  - Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, 
      No.678 Furong Road, Economic Development District, Hefei 230601, Anhui Province, 
      China.
FAU - Chen, Xueying
AU  - Chen X
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Xu, Banglong
AU  - Xu B
AD  - Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, 
      No.678 Furong Road, Economic Development District, Hefei 230601, Anhui Province, 
      China.
FAU - Luo, Zhidan
AU  - Luo Z
AD  - Department of Geriatrics, Chongqing People's Hospital, Chongqing, China.
FAU - Liang, Yi
AU  - Liang Y
AD  - Houston Methodist Research Institute, Center for Cardiovascular Regeneration, 
      Houston, TX, USA.
FAU - Fang, Sihua
AU  - Fang S
AD  - Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, 
      No.678 Furong Road, Economic Development District, Hefei 230601, Anhui Province, 
      China.
FAU - Li, Mengli
AU  - Li M
AD  - Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, 
      No.678 Furong Road, Economic Development District, Hefei 230601, Anhui Province, 
      China.
FAU - Wang, Xiaochen
AU  - Wang X
AD  - Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, 
      No.678 Furong Road, Economic Development District, Hefei 230601, Anhui Province, 
      China. Electronic address: whayde@21cn.com.
FAU - Lin, Xianhe
AU  - Lin X
AD  - Department of Cardiology, The First Affiliated Hospital of Anhui Medical 
      University, No.218 Jixi Road, Shushan District, Hefei city 230601, Anhui 
      Province, China. Electronic address: linxh_ah@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211105
PL  - Netherlands
TA  - J Cardiol
JT  - Journal of cardiology
JID - 8804703
RN  - 0 (Klf4 protein, mouse)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn92 microRNA, mouse)
SB  - IM
MH  - Animals
MH  - *Atherosclerosis/genetics/prevention & control
MH  - Kruppel-Like Factor 4/metabolism
MH  - *Macrophage Activation
MH  - Macrophages/metabolism
MH  - Mice
MH  - *MicroRNAs/genetics/metabolism
MH  - *Plaque, Atherosclerotic
OTO - NOTNLM
OT  - Atherosclerosis
OT  - KLF4
OT  - Macrophage polarization
OT  - miR-92
COIS- Declaration of Competing Interest None.
EDAT- 2021/11/10 06:00
MHDA- 2022/03/03 06:00
CRDT- 2021/11/09 05:52
PHST- 2021/07/27 00:00 [received]
PHST- 2021/10/06 00:00 [revised]
PHST- 2021/10/07 00:00 [accepted]
PHST- 2021/11/10 06:00 [pubmed]
PHST- 2022/03/03 06:00 [medline]
PHST- 2021/11/09 05:52 [entrez]
AID - S0914-5087(21)00289-6 [pii]
AID - 10.1016/j.jjcc.2021.10.015 [doi]
PST - ppublish
SO  - J Cardiol. 2022 Mar;79(3):432-438. doi: 10.1016/j.jjcc.2021.10.015. Epub 2021 Nov 
      5.