PMID- 28678311
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181202
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 21
IP  - 11
DP  - 2017 Jun
TI  - Regulation of miR-92a on vascular endothelial aging via mediating Nrf2-KEAP1-ARE 
      signal pathway.
PG  - 2734-2742
LID - 12894 [pii]
AB  - OBJECTIVE: Various human aging-related diseases start with vascular aging, in 
      which the aging of vascular endothelium is the first step to cause a structural 
      and functional deficit of vascular endothelium, leading to vascular disorders. 
      MicroRNA (miR) participates in various processes of body development and 
      pathological processes via mediating cell proliferation, differentiation, and 
      apoptosis. A previous study showed the correlation between cardiovascular disease 
      and miR-92a, whose role and mechanism in vascular endothelial aging has not been 
      reported. MATERIALS AND METHODS: In vitro, cultured human umbilical vein 
      endothelial cells (HUVECs) were prepared for the vascular endothelial aging model 
      by using 10-6 mM angiotensin II. MiR-92a expression was examined. After 
      transfecting with the miR-92a inhibitor, 
      3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was 
      employed to describe cell proliferation, and the Caspase 3 activity assay kit was 
      used to evaluate apoptosis activity. Myeloid peroxidase (MPO) and superoxidase 
      (SOD) activity, plus reactive oxygen species (ROS) content were measured. Nrf2, 
      KEAP1 and ARE mRNA expressions were measured by real-time PCR. Nuclear factor 
      erythroid 2 p45 related factor 2 (Nrf2) protein level, inflammatory factors tumor 
      necrosis factor alpha (TNF-alpha) and interleukin-2 (IL-2) were tested by western blot or 
      enzyme-linked immunosorbent assay (ELISA). RESULTS: In model group, miR-92a 
      expression was elevated significantly compared to the control group (p < 0 .05). 
      MiR-92a inhibitor transfection facilitated cell proliferation, decreased Caspase 
      3 activity, ROS or MPO, expressions of TNF-alpha, IL-2 and KEAP1, and enhanced SOD 
      level and Nrf2, ARE expressions significantly compared to the model group (p < 
      0.05). CONCLUSIONS: In aged vascular endothelium, miR-92a was up-regulated. 
      Through inhibiting miR-92a expression and regulating Nrf2-KEAP1-ARE signal 
      pathway, the oxidative stress reaction or inflammation can be suppressed, thus 
      inhibiting endothelial apoptosis and facilitating cell proliferation.
FAU - Liu, H
AU  - Liu H
AD  - Department of International Medical Health Care Center, Zhengzhou Yihe Hospital 
      Affiliated to Henan University, Zhengzhou, China. liuyiwanghb@163.com.
FAU - Wu, H-Y
AU  - Wu HY
FAU - Wang, W-Y
AU  - Wang WY
FAU - Zhao, Z-L
AU  - Zhao ZL
FAU - Liu, X-Y
AU  - Liu XY
FAU - Wang, L-Y
AU  - Wang LY
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (MIRN92 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 3.1.1.- (Carboxylic Ester Hydrolases)
RN  - EC 3.1.1.2 (arylesterase)
SB  - IM
MH  - Apoptosis
MH  - Carboxylic Ester Hydrolases/*metabolism
MH  - Cell Proliferation
MH  - *Cellular Senescence/genetics
MH  - Endothelium, Vascular/*metabolism/pathology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/*metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Signal Transduction
MH  - Up-Regulation
EDAT- 2017/07/06 06:00
MHDA- 2018/07/10 06:00
CRDT- 2017/07/06 06:00
PHST- 2017/07/06 06:00 [entrez]
PHST- 2017/07/06 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
AID - 12894 [pii]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2017 Jun;21(11):2734-2742.