Your browser doesn't support javascript.
loading
Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke.
Ye, Jing; Bi, Xinyuan; Deng, Shiyu; Wang, Xianghui; Liu, Ze; Suo, Qian; Wu, Jiao; Chen, Haoran; Wang, Yong; Qian, Kun; Shi, Rubing; Zhao, Jing; Yang, Guo-Yuan; Ye, Jian; Tang, Yaohui.
Afiliação
  • Ye J; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Bi X; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Deng S; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Wang X; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Liu Z; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Suo Q; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Wu J; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Chen H; Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • Wang Y; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Qian K; Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
  • Shi R; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Zhao J; Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • Yang GY; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
  • Ye J; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201102, China.
  • Tang Y; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
Theranostics ; 14(15): 6071-6087, 2024.
Article em En | MEDLINE | ID: mdl-39346547
ABSTRACT
Rationale Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear.

Methods:

Surface-enhanced Raman spectroscopy (SERS) and liquid chromatography-mass spectrometry (LC‒MS) analysis of clinical serum samples from 69 controls and 51 ischemic stroke patients who underwent reperfusion within 24 hours were performed to identify differentially abundant metabolites. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) and then intravenously injected with hypoxanthine. The infarct area was evaluated via tetrazolium chloride (TTC) staining, and behavior tests were conducted. Blood-brain barrier (BBB) leakage was assessed by Evans blue and IgG staining. Human blood vessel organoids were used to investigate the mechanism of hypoxanthine-induced pyroptosis of endothelial cells.

Results:

SERS and LC‒MS revealed the metabolic profiles of serum from stroke patients and controls with high sensitivity, speed and accuracy. Hypoxanthine levels were significantly elevated in the acute stage of ischemic stroke in both patients and mice (p < 0.001 after Bonferroni correction). In addition, increasing hypoxanthine increased the infarct area and aggravated BBB leakage and neurobehavioral deficits in mice after ischemic stroke. Further mechanistic studies using endothelial cells, human blood vessel organoids, and stroke mice demonstrated that hypoxanthine-mediated gasdermin E (GSDME)-dependent pyroptosis of endothelial cells occurs through intracellular Ca2+ overload.

Conclusion:

Our study identified hypoxanthine as an important metabolite that induces vascular injury and BBB disruption in stroke through triggering GSDME-dependent pyroptosis of endothelial cells.
Assuntos
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Biomarcadores / Hipoxantina / Células Endoteliais / Piroptose / AVC Isquêmico Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Theranostics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Austrália
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Barreira Hematoencefálica / Biomarcadores / Hipoxantina / Células Endoteliais / Piroptose / AVC Isquêmico Limite: Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Theranostics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Austrália