Transcriptome analysis reveals therapeutic potential of NAMPT in protecting against abdominal aortic aneurysm in human and mouse  

作　　者：Yu Ouyang Yimei Hong Cong Mai Hangzhen Yang Zicong Wu Xiaoyan Gao Weiyue Zeng Xiaohui Deng Baojuan Liu Yuelin Zhang Qingling Fu Xiaojia Huang Juli Liu Xin Li 

机构地区：[1]Department of Emergency Medicine,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangdong,510006,China [2]School of Medicine,South China University of Technology,Guangdong,510006,China [3]Otorhinolaryngology Hospital,The First Affiliated Hospital,Sun Yat-sen University,58 Zhongshan Road II,Guangzhou,510006,China [4]Extracellular Vesicle Research and Clinical Translational Center,The First Affiliated Hospital,Sun Yat-sen University,Guangdong,510006,China [5]Medical Research Institute,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,510080,China [6]Department of Emergency Medicine,The Key Laboratory of Advanced Interdisciplinary Studies,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510120,China [7]Global Health Research Center,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,510080,China

出　　处：《Bioactive Materials》2024年第4期17-36,共20页生物活性材料（英文）

基　　金：funded by the National Natural Science Grant of China(No.82072225,82272246);High-level Hospital Construction Project of Guangdong Provincial People’s Hospital(No.DFJHBF202104,No.DFJH201918);Science and Technology Program of Guangzhou,China(No.202206010044);Guangdong Basic and Applied Basic Research Foundation(2021B1515120062).

摘　　要：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.

关 键 词：Abdominal aorta Vascular smooth muscle cells SENESCENCE Oxidative phosphorylation Electron transport chain 

分 类 号：R73[医药卫生—肿瘤]