PMID- 34493702
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210915
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 7
IP  - 1
DP  - 2021 Sep 7
TI  - Effect of endothelial progenitor cell-derived extracellular vesicles on 
      endothelial cell ferroptosis and atherosclerotic vascular endothelial injury.
PG  - 235
LID - 10.1038/s41420-021-00610-0 [doi]
LID - 235
AB  - Atherosclerosis (AS) is a chronic inflammatory disorder characterized by 
      endothelial dysfunction. Endothelial progenitor cells (EPCs) can overcome 
      endothelial dysfunction and reduce AS risk. This study focused on the role of 
      EPC-secreted extracellular vesicles (EPC-EVs) in AS. First, mouse EPCs and mouse 
      aortic endothelial cells (MAECs) were isolated and identified. EVs were isolated 
      from EPCs and identified. EPC-EVs were co-cultured with MAECs and the 
      internalization of EVs was observed. Glutathione (GSH) consumption, reactive 
      oxygen species (ROS) production, lipid peroxidation, and iron accumulation and 
      cell death in endothelial cells were detected. The binding relationship between 
      miR-199a-3p and specificity protein 1 (SP1) was confirmed using dual-luciferase 
      and RIP assays. The mouse model of AS was established. The relationships between 
      miR-199a-3p expression and aortic area plaque and serum pro-inflammatory factor 
      were analyzed. The degree of atherosclerotic lesion was detected using oil red O 
      staining and the serum inflammatory factors were detected using ELISA. Our 
      results elicited that EPC-EVs inhibited cell death, GSH consumption, ROS 
      production, lipid peroxidation, and iron accumulation in endothelial cells, 
      thereby suppressing ferroptosis of endothelial cells. EPC-EVs transferred 
      miR-199a-3p into endothelial cells. miR-199a-3p targeted SP1. Silencing 
      miR-199a-3p or overexpression of SP1 in endothelial cells reversed the effect of 
      EPC-EVs on ferroptosis of endothelial cells. In vivo experiments confirmed that 
      EPC-EVs inhibited ferroptosis of endothelial cells and then alleviated the 
      occurrence of AS via the miR-199a-3p/SP1 axis. To conclude, EPC-EVs transferred 
      miR-199a-3p to inhibit SP1, thus repressing ferroptosis of endothelial cells and 
      retarding the occurrence of AS.
CI  - (c) 2021. The Author(s).
FAU - Li, Lin
AU  - Li L
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China.
FAU - Wang, Haining
AU  - Wang H
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China.
FAU - Chen, Xiao
AU  - Chen X
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China.
FAU - Zhang, Zhongwang
AU  - Zhang Z
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China.
FAU - Li, Qiang
AU  - Li Q
AD  - Department of Vascular Surgery, Qingdao Hiser Medical Center, 4 Renmin Road, 
      Shibei District, 266033, Qingdao City, Shandong Province, China. 
      QiangLi0114@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210907
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC8423825
COIS- The authors declare no competing interests.
EDAT- 2021/09/09 06:00
MHDA- 2021/09/09 06:01
PMCR- 2021/09/07
CRDT- 2021/09/08 06:17
PHST- 2021/05/31 00:00 [received]
PHST- 2021/07/26 00:00 [accepted]
PHST- 2021/06/22 00:00 [revised]
PHST- 2021/09/08 06:17 [entrez]
PHST- 2021/09/09 06:00 [pubmed]
PHST- 2021/09/09 06:01 [medline]
PHST- 2021/09/07 00:00 [pmc-release]
AID - 10.1038/s41420-021-00610-0 [pii]
AID - 610 [pii]
AID - 10.1038/s41420-021-00610-0 [doi]
PST - epublish
SO  - Cell Death Discov. 2021 Sep 7;7(1):235. doi: 10.1038/s41420-021-00610-0.