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This study investigates whether the RNA-binding protein SAMD4A suppresses VSMC phenotype switching and inhibits AAA formation. Single-cell RNA sequencing, together with in vivo pancreatic elastase (PPE)-induced mouse modeling, and mechanistic assays using RNA immunoprecipitation-seq and ChIP-qPCR, delineate regulation via KDM2B.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/samd4a-inhibits-abdominal-aortic-aneurysm-development-and-vsmc-phenotypic-transformation-through-targeting-kdm2b-research-summary/437438/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/samd4a-inhibits-abdominal-aortic-aneurysm-development-and-vsmc-phenotypic-transformation-through-targeting-kdm2b-research-summary/437438.png","ImageObject",300,407,{"name":92,"@type":93},"Grenda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",15,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main research goal of this study?","Question",{"text":113,"@type":114},"To determine whether the RNA-binding protein SAMD4A suppresses VSMC phenotypic transformation and inhibits abdominal aortic aneurysm formation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was the VSMC phenotypic heterogeneity during AAA formation studied?",{"text":118,"@type":114},"Single-cell RNA sequencing (scRNA-seq) was used to reveal smooth muscle cell phenotypic heterogeneity and RNA-binding protein dysregulation during AAA formation.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanism links SAMD4A to VSMC transformation and AAA development?",{"text":122,"@type":114},"SAMD4A regulates VSMC contraction by binding to KDM2B; KDM2B suppresses VSMC contractile marker transcription by reducing H3K4me3 and H3K36me2 levels at promoters.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},437438,1790763232,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":105,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},7971474921005,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Journal of Advanced Research 79 (2026) 223–237  \nContents lists available at ScienceDirect  \nJournal of Advanced Research  \njournal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare)  \nSAMD4A inhibits abdominal aortic aneurysm development and VSMC phenotypic transformation through targeting KDM2B  \nQing Chen a,b, 1, Shenrong Liu c, 1, Haobin Zhou c, 1, Junfen Wang f, Xiaoyong Xiao g, Guojun Chenh, Juan Dud, Lintao Zhong e,⁎, Haoyu Song d,⁎⁎, Xianying Huang a,⁎⁎⁎  \na Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515 Guangdong, China b Department of Vascular Surgery, Shenzhen Third People’s Hospital, the Second Affiliated Hospital, Southern University Science and Technology, China  \nc Department of Cardiology, the Key Laboratory of Advanced Interdisciplinary Studies Center, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120 Guangdong, China  \nd Department of Geriatrics, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China  \ne Department of Cardiology, the Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China  \nf Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China g Department of Emergency Medicine, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People’s Hospital, Shenzhen, Guangdong 518035, China  \nh Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China  \nh i g h l i g h t s  \n• SAMD4A inhibits AAA formation and VSMC phenotypic transformation.  \n• SAMD4A regulates VSMC phenotypic transformation by binding to KDM2B.  \n• KDM2B suppresses VSMC marker expression by reducing H3K4me3 and H3K36me2 levels.  \ng r a p h i c a l a b s t r a c t  \na r t i c l e i n f o  \nArticle history:  \nReceived 29 November 2024 Revised 1 March 2025  \nAccepted 10 March 2025  \nAvailable online 11 March 2025  \nKeywords: Aneurysm Smooth muscle cell  \na b s t r a c t  \nIntroduction: Abdominal aortic aneurysm (AAA) is a fatal vascular disease without effective drug treatments. Pathological vascular smooth muscle cell (VSMC) phenotypic transformation is the underlying cause of AAA. However, the underlying mechanism has not been fully elucidated.  \nObjective: We aimed to determine whether the RNA binding protein SAMD4A suppresses VSMC phenotype transformation and inhibits AAA formation.  \nMethods: Single-cell RNA sequencing (scRNA-seq) was conducted to reveal smooth muscle cell phenotypic heterogeneity and RNA-binding protein dysregulation during AAA formation. A pancreatic elastase (PPE)-induced mouse AAA model was generated to confirm the function of SAMD4A in vivo. RNA-seq  \n⁎ Corresponding author at: Department/Institute/Center/Division/Laboratory of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China.  \n⁎⁎ Corresponding author at: Department of Geriatrics, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Zhuhai 519000, China.⁎⁎⁎ Corresponding author at: Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China.  \nE-mail addresses: [zhonglintao1991@hotmail.com](zhonglintao1991@hotmail.com) (L. Zhong), [467869332@qq.com](467869332@qq.com) (H. Song), [18820148867@163.com](18820148867@163.com) (X. Huang).  \n1 These authors contributed equally to this work.  \n[https://doi.org/10.1016/j.jare.2025.03.018](https://doi.org/10.1016/j.jare.2025.03.018)  \n2090-1232/© 2025 The Authors. Published by Elsevier B.V. on behalf of Cairo University.  \nThis is an open access article under the CC BY","cbCaifJZfLgXGbpn","https://ap.wps.com/l/cbCaifJZfLgXGbpn","pdf",6281529,"English","# Article highlights\n## SAMD4A suppresses AAA formation and VSMC transformation\n## Mechanistic axis: SAMD4A–KDM2B–histone marks\n# Study design and methods\n## Single-cell RNA sequencing and RNA immunoprecipitation-seq\n## PPE-induced mouse AAA model\n## ChIP–qPCR for promoter regulation\n# Key results\n## VSMC subtype transformation during AAA formation\n## SAMD4A knockout and knock-in effects in vivo\n## KDM2B counters SAMD4A protection\n# Conclusions\n## Targeting KDM2B as a therapeutic rationale","[{\"question\":\"What is the main research goal of this study?\",\"answer\":\"To determine whether the RNA-binding protein SAMD4A suppresses VSMC phenotypic transformation and inhibits abdominal aortic aneurysm formation.\"},{\"question\":\"How was the VSMC phenotypic heterogeneity during AAA formation studied?\",\"answer\":\"Single-cell RNA sequencing (scRNA-seq) was used to reveal smooth muscle cell phenotypic heterogeneity and RNA-binding protein dysregulation during AAA formation.\"},{\"question\":\"What mechanism links SAMD4A to VSMC transformation and AAA development?\",\"answer\":\"SAMD4A regulates VSMC contraction by binding to KDM2B; KDM2B suppresses VSMC contractile marker transcription by reducing H3K4me3 and H3K36me2 levels at promoters.\"}]","SAMD4A inhibits abdominal aortic aneurysm development and VSMC phenotypic transformation through targeting KDM2B - Research summary | PDF",1790681855,38]