Cited by 19Nitric Oxide and Endothelin EffectsAutophagy in Disease and TherapyFolate and B Vitamins Research

Homocysteine up-regulates ET B receptors via suppression of autophagy in vascular smooth muscle cells

Chen, Yulong, Zhang, Hongmei, Liu, Huanhuan, Li, Ke, Su, Xingli·2018·Microvascular Research

Abstract

The change of autophagy is implicated in cardiovascular diseases (CVDs). Homocysteine (Hcy) up-regulates endothelin type B (ET B) receptors in vascular smooth muscle cells (VSMCs). However, it is unclear whether autophagy is involved in Hcy-induced-up-regulation of ET B receptors in VSMCs. The present study was designed to examine the hypothesis that Hcy up-regulates ET B receptors by inhibiting autophagy in VSMCs. Hcy treated the rat superior mesenteric artery (SMA) without endothelium in the presence and absence of AICAR, rapamycin or MHY1485 for 24 h. The contractile responses to sarafotoxin 6c (S6c) (an ET B receptor agonist) were studied using a sensitive myograph. Levels of protein expression were determined using Western blot analysis. Punctate staining of LC3B was exanimated by immunofluorescence using confocal microscopy. The results showed that Hcy inhibited AMPK, and activated mTOR, followed by impairing autophagy, and increased the levels of ET B receptor protein expression and the ET B receptor-mediated contractile responses to S6c in SMA without endothelium. However, these effects were reversed by AICAR or rapamycin. Additionally, MHY1485 up-regulated the AICAR-inhibited ET B receptor-mediated contractile response and the levels of ET B receptor protein expression in presence of Hcy. In conclusion, this suggested that Hcy up-regulated ET B receptors by inhibiting autophagy in VSMCs via AMPK/mTOR signaling pathway.

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Crossref · 10.1016/j.mvr.2018.03.010

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Authors
Chen, Y., Zhang, H., Liu, H., Li, K., & Su, X.
Affiliations
Xi'an Medical University (CN)
Corresponding author
  • Chen, Yulong
  • Su, Xingli
Venue
Microvascular Research
Publisher
Elsevier BV
Published
2018-09
Volume
119
Pages
13-21
ISSN
0026-2862 (ISSN-L)
OpenAlex
W2794471811
Cited by
19
References
30
Citations by year
2024: 1 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 5
FWCI
1.71
Type
journal article
Language
en
Open access
closed
Locations
  • Microvascular Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81500350)
  • Supporting Fund Project of Xi'an Medical University (2016PT27)
  • Education Department of Shaanxi Province (16JS098)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
Keywords
homocysteine, endothelin B receptor, autophagy, vascular smooth muscle cells, AMPK/mTOR signaling, MHY1485, AICAR, rapamycin, sarafotoxin S6c, vascular contractility, LC3B, cardiovascular disease
MeSH terms
Animals, Autophagy, Homocysteine, Humans, Muscle, Smooth, Vascular, Vasoconstriction, Signal Transduction, Up-Regulation, Rats, Sprague-Dawley, Mesenteric Artery, Superior, Myocytes, Smooth Muscle, Receptor, Endothelin B, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases, In Vitro Techniques

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