ReferenceID 2176
The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis
Atherosclerosis
BACKGROUND AND AIMS: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in t
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Record Fields
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- Reference Id
- 2176
- Evidence Id
- 18766
- Core Evidence Id
- 18766
- Source Reference Id
- 4404
- Herb2 Reference Id
- HBREF005201
- Subject Paper Key
- HBIN033053_34478920
- Pubmed Id
- 34478920
- Doi
- 10.1016/j.atherosclerosis.2021.08.015
- Paper Title
- The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis
- Paper Abstract
- BACKGROUND AND AIMS: Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. Macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1alpha (Ero1alpha) is critical for ER stress-induced apoptosis. We hypothesized that Ero1alpha may contribute to ER-stress induced macrophage apoptosis and plaque stability in advanced atherosclerotic lesions by HHcy. METHODS: Apoe-/- mice were maintained on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy atherosclerotic models. The role of Ero1alpha in atherosclerotic plaque stability, macrophage apoptosis and ER stress were monitored in the plaque of aortic roots in HHcy Apoe-/- mice with or without silence or overexpression of Ero1alpha through lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of Ero1alpha on ER stress dependent apoptosis in the presence of HHcy. RESULTS: Atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in Apoe-/- mice by high Hcy diet, accompanied by the upregulation of Ero1alpha expression and ER stress. Inhibition of Ero1alpha prevented macrophage apoptosis and atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1alpha deficiency, but enhanced by Ero1alpha overexpression. CONCLUSIONS: Hcy, via upregulation of Ero1alpha expression, activates ER stress-dependent macrophage apoptosis to promote vulnerable plaque formation in atherosclerosis. Ero1alpha may be a potential therapeutic target for atherosclerosis induced by Hcy.
- Journal
- Atherosclerosis
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Hhcy; Er-stress; Advanced Atherosclerotic Lesions; Hyperhomocysteinemia; Atherosclerosis; Ero1alpha Deficiency; Hhcy-aggravated Atherosclerosis
- Paper Title Cn
- Paper Title En
- The regulation of Ero1-alpha in homocysteine-induced macrophage apoptosis and vulnerable plaque formation in atherosclerosis
- Bilingual Status
- semi_complete