PMID- 35983375
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220820
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced 
      vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling 
      pathway.
PG  - 920977
LID - 10.3389/fphar.2022.920977 [doi]
LID - 920977
AB  - Vascular endothelial dysfunction (VED) is linked with the pathogenesis of 
      obstructive sleep apnea (OSA) comorbidities, such as cardiovascular disease. 
      Astragaloside IV (As-IV) has exhibited significant improvement for endothelial 
      dysfunction. Nonetheless, the protective mechanism is not clear. Therefore, the 
      present study investigated the potential mechanism of As-IV on VED. Calpain-1 
      knockout and wild-type C57BL/6 mice exposed to chronic intermittent hypoxia (CIH) 
      were established and treated with As-IV (40, 80 mg/kg) for 4 weeks. Human 
      coronary artery endothelial cells (HCAECs) subjected to CIH exposure were 
      pretreated with As-IV, MDL-28170 (calpain-1 inhibitor) and SRT1720 (SIRT1 
      activator) for 48 h in vitro. The endothelial function, inflammation, oxidative 
      stress and mitochondrial function were measured to evaluate VED. Our data 
      revealed that As-IV treatment ameliorated CIH-induced endothelial-dependent 
      vasomotion and augmented nitric oxide (NO) production. As-IV administration 
      suppressed the secretion of inflammation, oxidative stress and mitochondrial 
      dysfunction. As-IV treatment reduced the expression of calpain-1 and restored the 
      downregulated expression of SIRT1 and Thr(172) AMPK and Ser(1177) eNOS 
      phosphorylation. The effects of calpain-1 knockout and SRT1720 were similar to 
      the effect of As-IV on VED. These findings demonstrated that As-IV ameliorated 
      VED induced by chronic intermittent hypoxia via the calpain-1/SIRT1/AMPK 
      signaling pathway.
CI  - Copyright (c) 2022 Zhao, Meng, Wang, Fan, Liu, Zhang, Ran, Wang and Lu.
FAU - Zhao, Fang
AU  - Zhao F
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Meng, Yan
AU  - Meng Y
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Fan, Siqi
AU  - Fan S
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Liu, Yu
AU  - Liu Y
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Zhang, Xiangfeng
AU  - Zhang X
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Ran, Chenyang
AU  - Ran C
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Wang, Hongxin
AU  - Wang H
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
FAU - Lu, Meili
AU  - Lu M
AD  - Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning 
      Province, Jinzhou Medical University, Jinzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220802
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9381017
OTO - NOTNLM
OT  - Astragaloside IV
OT  - calpain-1
OT  - chronic intermittent hypoxia
OT  - oxidative stress
OT  - vascular endothelial dysfunction
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/20 06:00
MHDA- 2022/08/20 06:01
PMCR- 2022/08/02
CRDT- 2022/08/19 02:19
PHST- 2022/04/15 00:00 [received]
PHST- 2022/06/27 00:00 [accepted]
PHST- 2022/08/19 02:19 [entrez]
PHST- 2022/08/20 06:00 [pubmed]
PHST- 2022/08/20 06:01 [medline]
PHST- 2022/08/02 00:00 [pmc-release]
AID - 920977 [pii]
AID - 10.3389/fphar.2022.920977 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Aug 2;13:920977. doi: 10.3389/fphar.2022.920977. 
      eCollection 2022.