PMID- 33946046
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20210726
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 9
DP  - 2021 May 4
TI  - Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the 
      expression of KLF2.
PG  - 12996-13005
LID - 10.18632/aging.202973 [doi]
AB  - BACKGROUND: Oxidized LDL(Ox-LDL) mediated endothelial dysfunction is involved in 
      the pathogenesis of various cardiovascular diseases, including atherosclerosis. 
      Azilsartan is a potent agent for the treatment of hypertension as the antagonist 
      of the angiotensin II receptor. This study will investigate whether Azilsartan 
      possesses a beneficial effect against endothelial cell dysfunction induced by 
      ox-LDL and explore the underlying preliminary mechanism. METHODS: Ox-LDL was 
      applied to construct an in vitro endothelial dysfunction model in human umbilical 
      vascular endothelial cells (HUVECs). The expression of lectin-type oxidized LDL 
      receptor 1 (LOX-1), endothelial nitric oxide synthase (eNOS), tight junction 
      protein occludin, and transcriptional factor Kruppel-like factor 2 (KLF2) was 
      detected using qRT-PCR and Western blot. ELISA and qRT-PCR were utilized to 
      evaluate the production of chemokine monocyte chemotactic protein 1 (MCP-1) and 
      chemokine (C-X-C motif) Ligand 1 Protein (CXCL1) in treated HUVECs. The 
      generation of nitro oxide (NO) was determined using DAF-FM DA staining assay. 
      KLF2 was silenced by transfecting the cells with specific Small interfering RNA 
      (siRNA). FITC-dextran permeation assay was used to check the endothelial 
      monolayer permeability of treated HUVECs. RESULTS: Firstly, the elevated 
      expressions of LOX-1, MCP-1, and CXCL-1 induced by stimulation with ox-LDL were 
      significantly suppressed by Azilsartan. The downregulated eNOS and reduced 
      production of NO induced by ox-LDL were reversed by the introduction of 
      Azilsartan. Secondly, enlarged endothelial monolayer permeability and decreased 
      expression of occludin stimulated with ox-LDL were greatly reversed by treatment 
      with Azilsartan but were abolished by silencing the expression of KLF2. Lastly, 
      the inhibited expression of KLF2 induced by ox-LDL was significantly elevated by 
      the introduction of Azilsartan. CONCLUSION: Azilsartan might ameliorate 
      ox-LDL-induced endothelial damage via elevating the expression of KLF2.
FAU - Li, Wenfeng
AU  - Li W
AD  - Department of Cardiology, The First Affiliated Hospital of Jinan University, 
      Guangzhou 510630, Guangdong, China.
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Wang, Chenggao
AU  - Wang C
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Zhang, Dandan
AU  - Zhang D
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Zeng, Kanghua
AU  - Zeng K
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Xiao, Shihui
AU  - Xiao S
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Chen, Feng
AU  - Chen F
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
FAU - Luo, Jun
AU  - Luo J
AD  - Department of Cardiology, Ganzhou People's Hospital, Ganzhou 341000, Jiangxi, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210504
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Benzimidazoles)
RN  - 0 (KLF2 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Oxadiazoles)
RN  - 0 (oxidized low density lipoprotein)
RN  - F9NUX55P23 (azilsartan)
SB  - IM
MH  - Atherosclerosis/*drug therapy/metabolism/pathology
MH  - Benzimidazoles/*pharmacology/therapeutic use
MH  - Drug Evaluation, Preclinical
MH  - Endothelium, Vascular/drug effects/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Kruppel-Like Transcription Factors/*genetics
MH  - Lipoproteins, LDL/*metabolism
MH  - Oxadiazoles/*pharmacology/therapeutic use
PMC - PMC8148451
OTO - NOTNLM
OT  - Azilsartan
OT  - atherosclerosis
OT  - endothelial dysfunction
OT  - ox-LDL
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2021/05/05 06:00
MHDA- 2021/07/27 06:00
PMCR- 2021/05/15
CRDT- 2021/05/04 20:22
PHST- 2020/11/13 00:00 [received]
PHST- 2021/01/14 00:00 [accepted]
PHST- 2021/05/05 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2021/05/04 20:22 [entrez]
PHST- 2021/05/15 00:00 [pmc-release]
AID - 202973 [pii]
AID - 10.18632/aging.202973 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 May 4;13(9):12996-13005. doi: 10.18632/aging.202973. Epub 
      2021 May 4.