{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:09:22Z","timestamp":1788379762130,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["CIA160008"],"award-info":[{"award-number":["CIA160008"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Altered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory\u2010induced vascular\u2010mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug\u2010delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non\u2010CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sinonasal vascularity was increased significantly in CRSsNP and CRSwNP (<jats:italic>p<\/jats:italic> &lt; 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM\u20101)\u2012positive blood vessels. Pro\u2010angiogenic gene expression, including <jats:italic>PECAM1<\/jats:italic> and platelet\u2010activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (<jats:italic>p<\/jats:italic> &lt; 0.05). The fenestration sizes between endothelial cells (17\u2010280 nm) were larger in CRSwNP compared with CRSsNP (10\u201033 nm) patients and controls (4\u201012 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Significant increases in vascularity, the pro\u2010angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation\u2010driven vascular dysregulation in CRS pathology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22723","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T10:50:57Z","timestamp":1604314257000},"page":"976-983","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inflammation\u2010driven vascular dysregulation in chronic rhinosinusitis"],"prefix":"10.1002","volume":"11","author":[{"given":"Nitish","family":"Khurana","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah  Salt Lake City UT"},{"name":"Utah Center for Nanomedicine Nano Institute of Utah University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Pulsipher","sequence":"additional","affiliation":[{"name":"Utah Center for Nanomedicine Nano Institute of Utah University of Utah  Salt Lake City UT"},{"name":"Sinus and Skull Base Surgery Program Division of Otolaryngology\u2012Head and Neck Surgery Department of Surgery University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Jedrzkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaelene","family":"Ashby","sequence":"additional","affiliation":[{"name":"Sinus and Skull Base Surgery Program Division of Otolaryngology\u2012Head and Neck Surgery Department of Surgery University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea E.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Utah Center for Nanomedicine Nano Institute of Utah University of Utah  Salt Lake City UT"},{"name":"Sinus and Skull Base Surgery Program Division of Otolaryngology\u2012Head and Neck Surgery Department of Surgery University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidreza","family":"Ghandehari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah  Salt Lake City UT"},{"name":"Utah Center for Nanomedicine Nano Institute of Utah University of Utah  Salt Lake City UT"},{"name":"Sinus and Skull Base Surgery Program Division of Otolaryngology\u2012Head and Neck Surgery Department of Surgery University of Utah  Salt Lake City UT"},{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-5028","authenticated-orcid":false,"given":"Jeremiah A.","family":"Alt","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Chemistry University of Utah  Salt Lake City UT"},{"name":"Utah Center for Nanomedicine Nano Institute of Utah University of Utah  Salt Lake City UT"},{"name":"Sinus and Skull Base Surgery Program Division of Otolaryngology\u2012Head and Neck Surgery Department of Surgery University of Utah  Salt Lake City UT"},{"name":"Department of Biomedical Engineering University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","article-title":"Tissue remodelling in chronic rhinosinusitis\u2014review of literature","volume":"73","author":"Radajewski K","year":"2019","journal-title":"Otolaryngol Pol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000002998"},{"key":"e_1_2_7_4_1","first-page":"1199","article-title":"Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis","volume":"8","author":"Wang X","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.61"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599817737967"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh344"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-015-9477-2"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025203"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2007.01914.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0206-171"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/970890"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7141.1328"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(00)00125-8"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.88.53"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599815572097"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12253"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-008-9099-z"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq105"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13517"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"a016345","DOI":"10.1101\/cshperspect.a016345","article-title":"Inflammation and the blood microvascular system","volume":"7","author":"Pober JS","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"e_1_2_7_22_1","first-page":"1912","article-title":"Expressions of angiopoietins and Tie2 in human choroidal neovascular membranes","volume":"40","author":"Otani A","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022027"},{"issue":"1","key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1002\/alr.21695","article-title":"International Consensus Statement on Allergy and Rhinology: Rhinosinusitis","volume":"6","author":"Orlandi RR","year":"2016","journal-title":"Int Forum Allergy Rhinol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000239"},{"key":"e_1_2_7_26_1","first-page":"39","article-title":"Quantification of vascular density using a semiautomated technique for immunostained specimens","volume":"24","author":"King TW","year":"2002","journal-title":"Anal Quant Cytol Histol"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.3.965"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00215.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-019-0150-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111608"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2016.17"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4716"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1999.tb01785.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00524.2001"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00930"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213595"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.005"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-007-9074-0"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22723","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alr.22723","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22723","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T09:51:15Z","timestamp":1693561875000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.22723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/alr.22723"],"URL":"https:\/\/doi.org\/10.1002\/alr.22723","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]},"assertion":[{"value":"2020-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}