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Non\u2010healing skin wounds are associated with impaired angiogenesis and although the role of re\u2010establishing macroscopic blood flow to limbs to prevent wound chronicity is well investigated, less is known about vascular alterations at the microcirculatory level. We hypothesised that significant phenotypic changes would be evident in blood vessels surrounding chronic skin wounds. Wound edge tissue, proximal to wound (2\u2009cm from wound edge) and non\u2010involved skin (&gt;10\u2009cm from wound edge) was harvested under informed consent from 20 patients undergoing elective amputation due to critical limb ischemia. To assess blood vessel structure and viability, tissue was prepared for histological analysis and labelled with antibodies specific for PECAM\u20101 (CD31), CD146, endoglin, ALK\u20101, ALK\u20105, and p16<jats:sup>Ink4a<\/jats:sup> as a marker of cellular senescence. Density of microvasculature was significantly increased in wound edge dermis, which was concomitant with increased labelling for endoglin and CD146. The number of CD31 positive vessel density was unchanged in wound edge tissue relative to non\u2010involved tissue. Co\u2010labelling of endoglin with the transforming growth factor receptor ALK\u20101, and to a lesser extent ALK\u20105, demonstrated activation of endothelial cells which correlated with PCNA labelling indicative of proliferation. Analysis of p16<jats:sup>Ink4a<\/jats:sup> staining showed a complete lack of immunoreactivity in the vasculature and dermis, although staining was evident in sub\u2010populations of keratinocytes. We conclude that the endoglin\u2010ALK\u20101\u2010endothelial proliferation axis is active in the vasculature at the edge of chronic skin wounds and is not associated with p16<jats:sup>Ink4a<\/jats:sup> mediated senescence. This information could be further used to guide treatment of chronic skin wounds and optimise debridement protocols.<\/jats:p>","DOI":"10.1111\/wrr.13081","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T09:05:19Z","timestamp":1680685519000},"page":"321-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microcirculation surrounding <scp>end\u2010stage<\/scp> human chronic skin wounds is associated with endoglin\/<scp>CD146<\/scp>\/<scp>ALK<\/scp>\u20101 expression, endothelial cell proliferation and an absence of <scp>p16<sup>Ink4a<\/sup><\/scp>"],"prefix":"10.1111","volume":"31","author":[{"given":"Jiarong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anatomy &amp; Cell Biology University of Western Ontario  London Ontario Canada"},{"name":"Division of Vascular Surgery, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Tinney","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Cell Biology University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Grynyshyn","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; Cell Biology University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6474-3274","authenticated-orcid":false,"given":"J. 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