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Nonetheless, detailed documentation of specific vascular changes following SCI and targeted interventions for vascular treatment remains limited. This study demonstrates that traumatic pathological vascular remodeling occurs during the chronic phase of injury, characterized by enlarged vessel diameter, disruption of blood\u2010spinal cord barrier, endothelial\u2010to\u2010mesenchymal transition (EndoMT), and heightened extracellular matrix deposition. After SCI, osteopontin (OPN), a critical factor secreted by immune cells, is indispensable for early vascular regeneration but also contributes to traumatic pathological vascular remodeling. This work further elucidates the mechanism by which OPN influences spinal cord microvascular endothelial cells, involving Akt\u2010mediated Foxo1 phosphorylation. This process facilitates the extranuclear transport of Foxo1 and decreases Smad7 expression, leading to excessive activation of the TGF\u2010\u03b2 signaling pathway, which ultimately results in EndoMT and fibrosis. Targeted inhibition of Foxo1 phosphorylation through an endothelium\u2010specific aptamer\u2010liposome small molecule delivery system significantly mitigates vascular remodeling, thereby enhancing axon regeneration and neurological function recovery following SCI. The findings offer a novel perspective for drug therapies aimed at specifically targeting pathological vasculature after SCI.<\/jats:p>","DOI":"10.1002\/advs.202406398","type":"journal-article","created":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T16:20:19Z","timestamp":1727540419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Endothelial Foxo1 Phosphorylation Inhibition via Aptamer\u2010Liposome Alleviates OPN\u2010Induced Pathological Vascular Remodeling Following Spinal Cord Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Jiaqi","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Spine Surgery and Orthopaedics Xiangya Hospital Central South University Changsha 410008 China"},{"name":"Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan Province Changsha 410008 China"},{"name":"Department of Neurosurgery Xiangya Hospital Central South University 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