{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:09:49Z","timestamp":1789027789286,"version":"build-2803163510"},"reference-count":180,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Cutaneous keloids are pathological scars resulting from aberrant wound healing, characterized by infiltrative growth beyond the original wound margins and a failure to regress spontaneously. Although traditionally attributed to excessive extracellular matrix deposition and fibroblast proliferation, emerging evidence underscores the pivotal role of vascular dysregulation and endothelial dysfunction in keloid pathogenesis. This review systematically examines the endothelial cell system\u2014comprising vascular endothelial cells (VECs) and lymphatic endothelial cells (LECs)\u2014within the keloid microenvironment, focusing on how hypoxia, chronic inflammation, mechanical forces, sex hormones, the renin\u2013angiotensin system, and neuropeptides converge to drive structural and functional endothelial abnormalities. Special emphasis is placed on endothelial-to-mesenchymal transition (EndMT) as a critical pathway linking vascular pathology to fibrotic progression. Additionally, we comprehensively summarize current and emerging therapeutic strategies targeting the endothelium, including anti-angiogenic agents, HIF-1\u03b1 inhibition, EndMT blockade, mechanical offloading, hormonal modulation, renin\u2013angiotensin system (RAS) inhibition, and laser therapy. By providing an integrated overview of the endothelial mechanisms underlying keloid formation and persistence, this review aims to illuminate novel targets for therapeutic intervention and to inform the development of more effective clinical management strategies.<\/jats:p>","DOI":"10.3389\/fcell.2026.1919403","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:04:31Z","timestamp":1789027471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial system dysregulation underlies keloid development and therapeutic targeting"],"prefix":"10.3389","volume":"14","author":[{"given":"Yongxin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Plastic and Aesthetic Repair and Reconstruction, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juexian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Repair and Reconstruction, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Repair and Reconstruction, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Repair and Reconstruction, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Repair and Reconstruction, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0094822","DOI":"10.1128\/jcm.00948-22","article-title":"Performance of the JF5-Based galactomannoprotein EIA compared to the lateral flow device and the galactomannan EIA in serum and bronchoalveolar lavage fluid","volume":"60","author":"Aerts","year":"2022","journal-title":"J. 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