{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:57:58Z","timestamp":1787587078750,"version":"build-2736575974"},"reference-count":58,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL147472"],"award-info":[{"award-number":["R01HL147472"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL155934-01A1"],"award-info":[{"award-number":["R01HL155934-01A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R41HL164161"],"award-info":[{"award-number":["R41HL164161"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R56HL139559"],"award-info":[{"award-number":["R56HL139559"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Biol Rhythms"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from lungs of mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated a NOX2-NLRP3 signaling axis that drove inflammation as evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants (\n                    <jats:italic toggle=\"yes\">Bmal<\/jats:italic>\n                    1\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    and\n                    <jats:italic toggle=\"yes\">Cry1\/2<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome at baseline in the clock mutants, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.\n                  <\/jats:p>","DOI":"10.1177\/07487304251363656","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T03:59:02Z","timestamp":1757908742000},"page":"555-573","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Circadian Control of Pulmonary Endothelial Signaling Occurs via the NADPH Oxidase 2-NLRP3 Pathway"],"prefix":"10.1177","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5237-3835","authenticated-orcid":false,"given":"Shaon","family":"Sengupta","sequence":"first","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"},{"name":"Institute for Translational Medicine and Therapeutics (ITMAT), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Department of Neuroscience, Perelman School of Medicine, Chronobiology and Sleep Institute (CSI), University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-3342","authenticated-orcid":false,"given":"Yool","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Perelman School of Medicine, Chronobiology and Sleep Institute (CSI), University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Qin","family":"Tao","sequence":"additional","affiliation":[{"name":"Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Akolia","sequence":"additional","affiliation":[{"name":"Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Louneva","sequence":"additional","affiliation":[{"name":"Institute for Environmental Medicine and Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Forrest","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oindrila","family":"Paul","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-0079","authenticated-orcid":false,"given":"Thomas G","family":"Brooks","sequence":"additional","affiliation":[{"name":"Institute for Translational Medicine and Therapeutics (ITMAT), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R","family":"Grant","sequence":"additional","affiliation":[{"name":"Institute 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