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However, the mechanisms by which remote ischemic preconditioning (RIPC) may improve flap survival remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:bold>\n                        <jats:italic>METHODS<\/jats:italic>\n                      <\/jats:bold>\n                      :\n                    <\/jats:title>\n                    <jats:p>Rats were randomly assigned to three groups: sham, ischemia\/reperfusion (I\/R), and RIPC\u2009+\u2009I\/R. The I\/R model was established by ligating the iliopsoas and thoracodorsal arteries to induce flap ischemia, followed by reperfusion. RIPC was performed via limb clamping. A combination of high-throughput sequencing, functional cellular assays, and live imaging was used to assess gene expression, cellular functions, and flap viability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:bold>\n                        <jats:italic>RESULTS<\/jats:italic>\n                      <\/jats:bold>\n                      :\n                    <\/jats:title>\n                    <jats:p>\n                      RIPC upregulated the expression of ZNF667. This protein acted as a transcriptional repressor of\n                      <jats:italic>VHL<\/jats:italic>\n                      by binding to its promoter region, where it competitively inhibited the recruitment of histone-modifying enzymes, including MLL3\/4, SETD1A, and EP300. Consequently, histone methylation and acetylation were reduced, leading to suppressed\n                      <jats:italic>VHL<\/jats:italic>\n                      transcription. The downregulation of VHL diminished the ubiquitination-mediated degradation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), which in turn enhanced the expression of stromal cell-derived factor 1 (SDF1). This signaling cascade promoted the proliferation, migration, differentiation, and tube-forming capacity of endothelial progenitor cells (EPCs). Live imaging confirmed that RIPC stimulated the recruitment of EPCs into the flap tissue, accompanied by increased microvessel density. These effects collectively enhanced angiogenesis and significantly reduced the area of flap necrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:bold>\n                        <jats:italic>CONCLUSION<\/jats:italic>\n                      <\/jats:bold>\n                      :\n                    <\/jats:title>\n                    <jats:p>RIPC improves flap survival by modulating the ZNF667\u2013VHL\u2013SDF1 axis and augmenting the function of EPCs. These findings not only provide a potential therapeutic strategy for flap transplantation but also advance our understanding of the mechanisms underlying flap survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13770-026-00817-1","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T06:59:18Z","timestamp":1780729158000},"page":"881-899","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Remote Ischemic Preconditioning Enhances Skin Flap Survival via ZNF667\/SDF1-Mediated Endothelial Progenitor Cells Functions for Angiogenesis"],"prefix":"10.1007","volume":"23","author":[{"given":"Yuanbin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglei","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhu","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"817_CR1","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s10006-025-01378-8","volume":"29","author":"M Ooms","year":"2025","unstructured":"Ooms M, Winnand P, Heitzer M, Vohl N, Katz MS, Bickenbach J, et al. 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