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Here, we integrate single\u2010cell and spatial transcriptomic data from 110 thoracic aortic samples (80 individuals; control, aneurysm, dissection; 767\u00a0018 high\u2010quality cells) to generate a comprehensive thoracic\u2010aorta cellular\u2014molecular atlas. We identify an elastin\u2010rich fibroblast subset (Fibro_C1_FBN1+;\n                    <jats:italic>FBN1<\/jats:italic>\n                    ,\n                    <jats:italic>MFAP5<\/jats:italic>\n                    ,\n                    <jats:italic>LOX<\/jats:italic>\n                    ) that declines with age and is markedly depleted in AD, linking fibroblast loss to increased aortic wall vulnerability and dissection risk. Vascular smooth muscle cells (vSMCs) undergo\n                    <jats:italic>ENO1<\/jats:italic>\n                    \u2010driven glycolytic reprogramming under hypoxia, lose contractility and adopt a synthetic,\n                    <jats:italic>MIF<\/jats:italic>\n                    \u2010secreting phenotype that engages macrophage receptors to promote macrophage recruitment and pro\u2010inflammatory polarization, leading aggregated macrophages to upregulate proteolytic and fibrinolytic pathways and thereby accelerate extracellular\u2010matrix degradation. In vitro and in vivo,\n                    <jats:italic>ENO1<\/jats:italic>\n                    knockdown inhibits vSMC switching, reduces macrophage inflammation, and slows AD progression. This stromal\u2010immune axis suggests potential therapeutic targets in AD.\n                  <\/jats:p>","DOI":"10.1002\/advs.75509","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T18:07:07Z","timestamp":1778436427000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated Single\u2010Cell and Spatial Analysis Reveals a Metabolic\u2010Immune Axis Driving Aortic Dissection"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-3349","authenticated-orcid":false,"given":"Jing","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Cardiology People's Hospital of Xinjiang Uygur Autonomous Region  Urumqi Xinjiang China"},{"name":"Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research  Urumqi Xinjiang 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