PMID- 33340492
OWN - NLM
STAT- MEDLINE
DCOM- 20210615
LR  - 20210615
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 399
IP  - 1
DP  - 2021 Feb 1
TI  - Endothelium-specific endothelin-1 expression promotes pro-inflammatory macrophage 
      activation by regulating miR-33/NR4A axis.
PG  - 112443
LID - S0014-4827(20)30696-0 [pii]
LID - 10.1016/j.yexcr.2020.112443 [doi]
AB  - The hallmark of atherogenesis is characterized as endothelial dysfunction and 
      subsequent macrophage activation. Although our previous study has demonstrated 
      that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying 
      mechanism remains deeply investigation. Enhanced atherosclerotic plaques were 
      observed in endothelium-specific ET-1 overexpression ApoE(-/-) mice 
      (eET-1/ApoE(-/-)) concomitant with increased secretion of pro-inflammatory 
      adhesion molecules and cytokines. The conditional media used for culturing human 
      umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to 
      OX-LDL stimulation, was collected and utilized for bone marrow-derived 
      macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression 
      related to classical M1 macrophages but decreased alternative activated M2 
      macrophages genes expression in macrophage culturing with the conditional media. 
      Furthermore, consistent regulations of macrophage polarization were observed 
      using isolated exosomes from the conditional media. More importantly, we noticed 
      that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, 
      while bioinformatics analysis further indicated that miR-33 directly targeted 
      NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific 
      ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such 
      effects could be reversed by ET-1 knockdown. Taken together, our study indicated 
      that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to 
      macrophages and subsequently promote pro-inflammatory macrophage activation by 
      directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A 
      axis was the important mechanism underlying the effect of ET-1 on macrophage 
      activation and indicated that ET-1 may act as a promising target for 
      atherosclerosis management.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zhang, Juan
AU  - Zhang J
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China. Electronic address: 
      zhang_juan_bj@126.com.
FAU - Zhao, Wen-Shu
AU  - Zhao WS
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China.
FAU - Xu, Lin
AU  - Xu L
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China.
FAU - Wang, Xin
AU  - Wang X
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China.
FAU - Li, Xiao-Li
AU  - Li XL
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China.
FAU - Yang, Xin-Chun
AU  - Yang XC
AD  - Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang 
      Hospital, Capital Medical University, Beijing, 100020, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201216
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Endothelin-1)
RN  - 0 (MIRN33a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NR4A1 protein, human)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Embryo, Mammalian
MH  - Endothelin-1/*genetics/metabolism
MH  - Endothelium, Vascular/*metabolism
MH  - HEK293 Cells
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Humans
MH  - Macrophage Activation/*genetics
MH  - Macrophages/metabolism/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/*genetics/metabolism
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/*genetics/metabolism
MH  - Organ Specificity/genetics
MH  - Signal Transduction/genetics
OTO - NOTNLM
OT  - Endothelial-1
OT  - HUVECs
OT  - Macrophages
OT  - NR4A
OT  - miR-33
EDAT- 2020/12/20 06:00
MHDA- 2021/06/16 06:00
CRDT- 2020/12/19 20:08
PHST- 2020/09/13 00:00 [received]
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/12/12 00:00 [accepted]
PHST- 2020/12/20 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/12/19 20:08 [entrez]
AID - S0014-4827(20)30696-0 [pii]
AID - 10.1016/j.yexcr.2020.112443 [doi]
PST - ppublish
SO  - Exp Cell Res. 2021 Feb 1;399(1):112443. doi: 10.1016/j.yexcr.2020.112443. Epub 
      2020 Dec 16.