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Neutrophil extracellular traps induced by IL-1ß promote endothelial dysfunction and aggravate limb ischemia.
Lin, Shigang; Zhu, Pengwei; Jiang, Liujun; Hu, Yujian; Huang, Lirui; He, Yangyan; Zhang, Hongkun.
Afiliación
  • Lin S; Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Zhu P; Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Jiang L; Department of Cardiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Hu Y; Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Huang L; Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • He Y; Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. heyangyan19881022@163.com.
  • Zhang H; Department of Vascular Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 1198050@zju.edu.cn.
Hypertens Res ; 47(6): 1654-1667, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38605142
ABSTRACT
Vascular inflammation and endothelial dysfunction contribute to vascular diseases. While neutrophil extracellular traps (NETs) participate in some vascular pathologies, their roles in lower limb ischemia remain poorly defined. This study investigated the functional significance of NETs in vascular inflammation and remodeling associated with limb ischemia. Single-cell RNA sequencing (scRNA-seq) and flow cytometry revealed neutrophil activation and upregulated NETs formation in human limb ischemia, with immunofluorescence confirming IL-1ß-induced release of NETs for vascular inflammation. Endothelial cell activation was examined via scRNA-seq and western blotting, indicating enhanced proliferation, expression of adhesion molecules (VCAM-1, ICAM-1), inflammatory cytokines (IL-1ß, IL-6) and decreased expression of VE-cadherin, that could be mediated by NETs to exacerbate endothelial inflammation. Mechanistically, NETs altered endothelial cell function via increased pSTAT1/STAT1 signaling. Vascular inflammation and subsequent ischemia were alleviated in vivo by NETosis or IL-1ß inhibition in ischemic mice. IL-1ß-NETs induce endothelial activation and inflammation in limb ischemia by stimulating STAT1 signaling. Targeting NETs may thus represent a novel therapeutic strategy for inflammatory vascular diseases associated with limb ischemia. Graphical abstract of NETs regulation of the development of vascular inflammation in lower limb ischemia via pSTAT1/STAT1 signaling pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-1beta / Trampas Extracelulares / Isquemia Límite: Animals / Humans / Male Idioma: En Revista: Hypertens Res Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-1beta / Trampas Extracelulares / Isquemia Límite: Animals / Humans / Male Idioma: En Revista: Hypertens Res Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido