Homocysteine up-regulates endothelin type A receptor in vascular smooth muscle cells through Sirt1/ERK1/2 signaling pathway
Abstract
Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ET A ) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ET A receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ET A receptor through the Sirt1/ERK1/2 signaling pathway. In vitro experiments were performed in the rat superior mesenteric artery. The rat superior mesenteric artery was cultured with or without homocysteine (Hcy) in the presence and absence of Resveratrol (Res, a Sirt1 agonist), SRT1720 (a specific Sirt1 agonist) or U0126 (an ERK1/2 signaling pathway inhibitor) in serum-free medium for 24h. In vivo, the rats received subcutaneous injections of Hcy in the presence of or absence of Res or U0126 for 3weeks. The contractile response to ET-1 was studied using a sensitive myograph. In addition, the level of protein expression was determined using western blotting. Hcy significantly increased the expression of ET A receptor and also increased the ET A receptor-mediated contractile response induced by ET-1 in vitro. These effects were inhibited by Res, SRT1720 and U0126 treatment. In addition, Hcy down-regulated the level of Sirt1, and up-regulated the leve…
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SIRT1 activation is an effective approach to manage hyperhomocysteinemia-induced oxidative stress.
“Previous reports have suggested that SIRT1 activation is an effective approach to manage HHcy‐induced oxidative stress,33, 34”
From Picroside <scp>II</scp> attenuates hyperhomocysteinemia‐induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis (2019) · cites this paper as [34]
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- Authors
- Chen, Y., Liu, H., Wang, X., Zhang, H., Liu, E., & Su, X.
- Affiliations
- Xi'an Medical University (CN)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Xi'an Jiaotong University (CN)
- Corresponding author
- Chen, Yulong
- Su, Xingli
- Venue
- Microvascular Research
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 114
- Pages
- 34-40
- ISSN
- 0026-2862 (ISSN-L)
- OpenAlex
- W2620681278
- Cited by
- 23
- References
- 33
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 6 · 2018: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microvascular Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81500350)
- Key Scientific Research Plan Project of Education Department of Shaanxi Province (16JS096)
- China Postdoctoral Science Foundation (2015M582607)
- Natural Science Basic Research Plan in Shaanxi Province (2016JM8059)
- Shaanxi Postdoctoral Sustentation Fund (59)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- homocysteine, hyperhomocysteinemia, ETA receptor, vascular smooth muscle cells, SIRT1, ERK signaling, resveratrol, SRT1720, endothelin-1, vascular contractility, blood pressure, cardiovascular risk factors
- MeSH terms
- Animals, Cells, Cultured, Dose-Response Relationship, Drug, Homocysteine, Male, Muscle, Smooth, Vascular, Phosphorylation, Vasoconstriction, Signal Transduction, Up-Regulation, Rats, Sprague-Dawley, Mesenteric Artery, Superior, Mitogen-Activated Protein Kinase 1, Myocytes, Smooth Muscle, Receptor, Endothelin A, Protein Kinase Inhibitors, Mitogen-Activated Protein Kinase 3, Sirtuin 1, Histone Deacetylase Inhibitors
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