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However, the molecular link between Klf5, Golph3l, and Golgi morphology alteration in the context of the aneurysm is unclear. Here, we show that apoptosis\u2010induced proliferation (AIP) in VSMCs occurs in aortic dissection (AD) and aortic aneurysm of humans and mice. Golph3l upregulation by Klf5 facilitates TNF\u2010\u03b1 and TNFSF12 secretion from AngII\u2010stimulated VSMCs by inducing Golgi compaction, which is essential for AIP and aneurysm development. Mechanistically, AngII\u2010induced elevation of global m6A RNA level, especially m6A\u2010Gm40097, is responsible for Golph3l upregulation and AIP in VSMCs. Further, m6A\u2010Gm40097 mediates Klf5 interaction with Ythdc1 and p300 to form a transcription complex on the Golph3l promoter, thus activating transcription. Finally, a predictive website for post\u2010operative short\u2010term death is built based on AD patient's features, providing a platform to be able to predict risk stratification of AD patients. Collectively, this study identifies a novel lncRNA m6A modification\u2010dependent regulatory mechanism of chromatin remodeling and transcription activation. Targeting the Ythdc1\u2010p300\u2010Klf5 complex may serve as potential therapeutic strategy to improve Golgi dysfunction and aortic aneurysm.<\/jats:p>","DOI":"10.1002\/advs.202512116","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T21:29:36Z","timestamp":1764451776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ythdc1\u2010p300\u2010Klf5 Complex\u2010Mediated Golgi Dysfunction Promotes Aortic Aneurysm"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0169-0708","authenticated-orcid":false,"given":"Wen\u2010Li","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Key Laboratory of Neural and Vascular Biology Ministry of Education and Hebei Key Laboratory of Cardiovascular Homeostasis and Aging Hebei Medical University  Shijiazhuang Hebei 050017 China"},{"name":"Department of 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