IRF-1 promotes diabetic vasculopathy by mediating endothelial cell pyroptosis.

IF 1.4 4区 医学 Q3 PERIPHERAL VASCULAR DISEASE
Yande Zhou, Zhihua Liu, Yangyufan Xu, Jiadong Chen, Jianhui Li, Mingchen Zhang, Mingqi Weng, Xueqin Cao, Ying Xie
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引用次数: 0

Abstract

Background: Diabetic vasculopathy is not only one of the most common and serious complications of diabetes mellitus (DM) but also the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Endothelial cells, located at the interface between blood and interstitial tissues, are the first line of defense of the vascular system against inflammatory damage, and their death is usually linked to atherosclerosis progression. However, the exact mechanisms need to be explored in greater depth.

Methods: GSE169332 data, including one group of no diabetic atherosclerosis and one group of diabetic atherosclerosis, were integrated and analyzed using single-cell RNA sequencing (scRNA-seq) technology. The biological pathways involved and the key factor interferon regulatory factor 1 (IRF-1) were explored by Gene Ontology (GO) pathway enrichment and trajectory analysis. The role of IRF-1-mediated endothelial cell pyroptosis in diabetic model mice BKS-db/db was verified by in vivo assays of immunofluorescence, immunohistochemistry (IHC), hematoxylin and eosin (H&E) staining, and Masson staining.

Results: ScRNA-seq results showed that the development of diabetic vasculopathy was associated with endothelial cell pyroptosis, and Endothelial pyroptosis 1 cells(EP1)with high expression of pyroptosis-associated factors exhibited a significant increase in diabetic atherosclerosis samples. The GO enrichment results further emphasized the importance of endothelial cells in the progression of diabetic vasculopathy, especially EP1 cells. Trajectory analysis revealed that IRF-1 was more likely to be the hub gene of EP1 relative to other pyroptosis-related genes. Immunofluorescence, IHC, H&E staining, and Masson staining of mouse vascular tissues demonstrated that IRF-1 expression was significantly increased in diabetic model mice BKS-db/db, and the expression of pyroptosis-related marker NLRP3, as well as IL-1β and IL-18 levels, was also significantly increased.

Conclusion: IRF-1 promotes the progression of diabetic vasculopathy by mediating endothelial cell pyroptosis through increasing the expression of pyroptosis-related marker NLRP3 and the levels of IL-1β and IL-18.

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来源期刊
CiteScore
3.00
自引率
13.30%
发文量
603
审稿时长
50 days
期刊介绍: Annals of Vascular Surgery, published eight times a year, invites original manuscripts reporting clinical and experimental work in vascular surgery for peer review. Articles may be submitted for the following sections of the journal: Clinical Research (reports of clinical series, new drug or medical device trials) Basic Science Research (new investigations, experimental work) Case Reports (reports on a limited series of patients) General Reviews (scholarly review of the existing literature on a relevant topic) Developments in Endovascular and Endoscopic Surgery Selected Techniques (technical maneuvers) Historical Notes (interesting vignettes from the early days of vascular surgery) Editorials/Correspondence
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