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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recalcitrant nasal polyps are hallmarks of eosinophilic chronic rhinosinusitis, with abnormal fibrin deposition being critical for nasal polyp development. However, the specific cellular and molecular mechanisms underlying the pathogenesis of nasal polyps in patients with eosinophilic chronic rhinosinusitis remain poorly understood. To assess the impact of the renin-angiotensin system on eosinophilic chronic rhinosinusitis pathogenesis and identify new therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Renin-angiotensin system components, fibrin, tissue factor, and macrophages in nasal tissues were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and immunofluorescence. Gene expression and protein levels were also analyzed in cultured THP-1 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In eosinophilic chronic rhinosinusitis nasal polyps, angiotensin-converting enzyme 2, Mas receptor, and angiotensin (1\u20137) were significantly reduced, while angiotensin II receptor type 1 was increased compared to non-eosinophilic chronic rhinosinusitis nasal polyps. This suggests angiotensin II\/angiotensin II receptor type 1 axis predominance over the angiotensin (1\u20137)\/Mas receptor axis in eosinophilic chronic rhinosinusitis. Immunofluorescence revealed profound fibrin deposition and increased tissue factor levels in eosinophilic chronic rhinosinusitis nasal polyps. M2 macrophages (CD68\u2009+\u2009\/CD163\u2009+) were highly infiltrated, with most expressing tissue factor. Tissue factor expression was significantly increased in M2-polarized macrophages, and co-stimulation with angiotensin II further enhanced this expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Renin-angiotensin system dysregulation might contribute to nasal polyp development in patients with eosinophilic chronic rhinosinusitis. Angiotensin II\/angiotensin II receptor type 1 axis predominance over the angiotensin (1\u20137)\/Mas receptor axis may enhance fibrin deposition by enhancing tissue factor expression in M2 macrophages, contributing to recalcitrant nasal polyp formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02254-1","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:40:57Z","timestamp":1777408857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renin\u2013angiotensin imbalance promotes excessive fibrin deposition through M2 macrophage\u2013derived tissue factor expression in eosinophilic chronic rhinosinusitis"],"prefix":"10.1007","volume":"75","author":[{"given":"Tetsuji","family":"Takabayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukinori","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Sakashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Fujieda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"2254_CR1","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.jaci.2020.01.027","volume":"145","author":"T Takabayashi","year":"2020","unstructured":"Takabayashi T, Schleimer RP. 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