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Therapeutic revascularization, including angiogenic and arteriogenic therapy, is a promising treatment approach for peripheral arterial disease. However, the progress of clinical trials is not ideal, possibly due to insufficiency of preclinical models, such as not taking into account the effect of aging on vascular regeneration. Macrophages are crucial in angiogenesis and arteriogenesis. The aging microenvironment typically makes recruited monocytes and macrophages more susceptible to senescence. However, the feature of macrophages in ischemic hindlimb muscle of old individuals and their underlying role remains unclear. In this study, we reveal that macrophages of ischemic skeletal muscle in old mice are more senescent and proinflammatory. By transplanting macrophages into mice following hindlimb ischemia, we find senescent macrophages inhibit revascularization. Mechanistically, these senescent macrophages induce endothelial dysfunction via increasing vascular endothelial growth factor A\u2010165B (VEGF\u2010A165B) expression and secretion, and eventually impair revascularization. Notably, plasma VEGF\u2010A165B levels are elevated in old patients with PAD and positively associated with a lower ankle brachial index (ABI). Our study suggests that targeting the senescent macrophages presents an avenue to improve age\u2010related revascularization damage.<\/jats:p>","DOI":"10.1111\/acel.70059","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T07:26:57Z","timestamp":1744874817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Senescent Macrophages Promote Age\u2010Related Revascularization Impairment by Increasing Antiangiogenic\n                    <scp>VEGF<\/scp>\n                    \u2010\n                    <scp>A165B<\/scp>\n                    Expression"],"prefix":"10.1111","volume":"24","author":[{"given":"Minghong","family":"Chen","sequence":"first","affiliation":[{"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 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