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Using an enzyme\u2010linked immunosorbent assay, we found that plasma IL\u201017A levels were similar in young and aged groups in both PAD patients and mice with hindlimb ischemia. In contrast, IL\u201017F levels were elevated in the aged group. Spearman correlation analysis showed a positive correlation between IL\u201017F levels and PAD severity, onset risk, and cardiovascular outcome. Under simulated ischemic conditions, IL\u201017F induced endothelial cells (ECs) senescence and dysfunction in a dose\u2010dependent manner. In aged male and female mice following left femoral artery ligation, results from Doppler imaging, ischemia and motor scores, and histology indicated that neutralization of IL\u201017F enhanced blood flow recovery, reduced ischemia scores, improved motor scores, and facilitated muscle regeneration and repair. Micro\u2010CT, whole\u2010mounting, and immunofluorescence staining results showed that neutralization of IL\u201017F promoted neovascularization and inhibited ischemic hindlimb muscle ECs' senescence and dysfunction. This study reveals for the first time that higher IL\u201017F levels were positively associated with PAD severity, onset risk, and cardiovascular outcome. Neutralization of IL\u201017F promoted postischemic neovascularization in aged mice, suggesting it represented a promising therapeutic strategy for elderly PAD patients.<\/jats:p>","DOI":"10.1096\/fj.202501109rr","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T15:35:02Z","timestamp":1762529702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interleukin\u2010\n                    <scp>17F<\/scp>\n                    Induces Ischemic Injury in Aged Mice by Causing Endothelial Cells' Senescence and Dysfunction"],"prefix":"10.1096","volume":"39","author":[{"given":"Minghong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of Geriatric Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of Geriatric Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of General &amp; Vascular Surgery, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilian","family":"Yao","sequence":"additional","affiliation":[{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-5842","authenticated-orcid":false,"given":"Yongping","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of Geriatric Medicine, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Center of Coronary Circulation, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00663-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.124.035923","article-title":"miRNA\u20106236 Regulation of Postischemic Skeletal Muscle Angiogenesis","volume":"13","author":"Mani A. 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