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Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse.
Ouyang, Yu; Hong, Yimei; Mai, Cong; Yang, Hangzhen; Wu, Zicong; Gao, Xiaoyan; Zeng, Weiyue; Deng, Xiaohui; Liu, Baojuan; Zhang, Yuelin; Fu, Qingling; Huang, Xiaojia; Liu, Juli; Li, Xin.
Afiliación
  • Ouyang Y; Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, 510006, China.
  • Hong Y; Department of Emergency Medicine, The Key Laboratory of Advanced Interdisciplinary Studies , The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
  • Mai C; Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, 510006, China.
  • Yang H; School of Medicine, South China University of Technology, Guangdong, 510006, China.
  • Wu Z; Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, 510006, China.
  • Gao X; School of Medicine, South China University of Technology, Guangdong, 510006, China.
  • Zeng W; Department of Emergency Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, 510006, China.
  • Deng X; Global Health Research Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
  • Liu B; Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510006, China.
  • Zhang Y; Extracellular Vesicle Research and Clinical Translational Center, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, 510006, China.
  • Fu Q; School of Medicine, South China University of Technology, Guangdong, 510006, China.
  • Huang X; School of Medicine, South China University of Technology, Guangdong, 510006, China.
  • Liu J; Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510006, China.
  • Li X; Extracellular Vesicle Research and Clinical Translational Center, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, 510006, China.
Bioact Mater ; 34: 17-36, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38173843
ABSTRACT
Abdominal Aortic Aneurysm (AAA) is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta, which has no effective therapeutic approaches due to unclear molecular mechanisms. Using single-cell RNA sequencing, we analyzed the molecular profile of individual cells within control and AAA abdominal aortas. We found cellular heterogeneity, with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells (VSMCs) in AAA. Up-regulated genes in AAA were associated with muscle tissue development and apoptosis. Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA. Additionally, VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation. Similar observations were made in a mouse model of AAA induced by Angiotensin II, further affirming the relevance of our findings to human AAA. The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention. Nicotinamide phosphoribosyltransferase (NAMPT, also named VISFATIN) signaling emerged as a signature event in AAA. NAMPT was significantly downregulated in AAA. NAMPT-extracellular vesicles (EVs) derived from mesenchymal stem cells restored NAMPT levels, and offered protection against AAA. Furthermore, NAMPT-EVs not only repressed injuries, such as cell senescence and DNA damage, but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models, suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment. These findings shed light on the cellular heterogeneity and injuries in AAA, and offered promising therapeutic intervention for AAA treatment.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: China