{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:09:03Z","timestamp":1740146943315,"version":"3.37.3"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2016T064"],"award-info":[{"award-number":["2016T064"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003246","name":"Dutch research council","doi-asserted-by":"crossref","award":["Veni Grant 2019"],"award-info":[{"award-number":["Veni Grant 2019"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013347","name":"European Society of Intensive Care Medicine","doi-asserted-by":"publisher","award":["Basic research Award 2021"],"award-info":[{"award-number":["Basic research Award 2021"]}],"id":[{"id":"10.13039\/501100013347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Society of Anaesthesiology and Intensive Care","award":["Research project grant 2022"],"award-info":[{"award-number":["Research project grant 2022"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nThe endothelial angiopoietin\/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin\/Tie2 system and edema formation.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nAdult male and female heterozygous Tie2 knockout mice (Tie2+\/\u2212<\/jats:sup>) and wild-type controls (Tie2+\/+<\/jats:sup>) were included (n = 9 per group). Renal and pulmonary injury were determined by wet\/dry weight ratio and H&E staining of tissue sections. Protein levels were studied in plasma by ELISA and pulmonary and renal mRNA expression levels by RT-qPCR.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nIn Tie2+\/+<\/jats:sup> mice, females had higher circulating angiopoietin-2 (138%, p<0.05) compared to males. Gene expression of angiopoietin-1 (204%, p<0.01), angiopoietin-2 (542%, p<0.001) were higher in females compared to males in kidneys, but not in lungs. Gene expression of Tie2, Tie1 and VE-PTP were similar between males and females in both organs. Renal and pulmonary wet\/dry weight ratio did not differ between Tie2+\/+<\/jats:sup> females and males. Tie2+\/+<\/jats:sup> females had lower circulating NGAL (41%, p<0.01) compared to males, whereas renal NGAL and KIM1 gene expression was unaffected.<\/jats:p>\nInterestingly, male Tie2+\/-<\/jats:sup> mice had 28% higher renal wet\/dry weight ratio (p<0.05) compared to Tie2+\/+<\/jats:sup> males, which was not observed in females nor in lungs. Partial deletion of Tie2 did not affect circulating angiopoietin-1 or angiopoietin-2, but soluble Tie2 was 44% and 53% lower in males and females, respectively, compared to Tie2+\/+<\/jats:sup> mice of the same sex. Renal and pulmonary gene expression of angiopoietin-1, angiopoietin-2, estrogen receptors and other endothelial barrier regulators was comparable between Tie2+\/-<\/jats:sup> and Tie2+\/+<\/jats:sup> mice in both sexes.<\/jats:p>\n<\/jats:sec>\n\nConclusion<\/jats:title>\nFemale sex seems to protect against renal, but not pulmonary edema in heterozygous Tie2 knock-out mice. This could not be explained by sex dimorphism in the endothelial angiopoietin\/Tie2 system.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0293673","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T18:25:30Z","timestamp":1700159130000},"page":"e0293673","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Female sex protects against renal edema, but not lung edema, in mice with partial deletion of the endothelial barrier regulator Tie2 compared to male sex"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6552-0830","authenticated-orcid":true,"given":"Anoek L. 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