{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:53:28Z","timestamp":1775822008381,"version":"3.50.1"},"reference-count":54,"publisher":"Portland Press Ltd.","issue":"4","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circadian clock genes, such as BMAL1 (brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1), CLOCK (circadian locomotor output cycles kaput), PER1\/2\/3 (period 1\/2\/3), and CRY1\/2 (cryptochrome 1\/2), can play crucial roles in regulating cardiovascular and renal functions, potentially via influencing salt sensitivity and blood pressure regulation. This thematic review elucidates the complex interaction between salt sensitivity, genetic variations in circadian rhythm genes, and systemic hypertension. We have particularly focused on the profound impact of obstructive sleep apnea (OSA), which has two key components\u2014intermittent hypoxia and sleep fragmentation\u2014on the pathophysiologic processes of hypertension. Circadian disruption may exacerbate hypertension through mechanisms involving hypoxia-induced gene regulation mainly via hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1). As our understanding of these genetic and pathophysiological interactions of circadian rhythm regulation deepens, more personalized treatment approaches for salt-sensitive hypertension may be possible. Interestingly, conditioning with controlled moderate intermittent hypoxia may elicit beneficial effects in the heart and vasculatures, possibly involving modulation of PER2, HIF-1\u03b1, and BMAL1 expression. It is feasible that in addition to the conventional therapies such as continuous positive airway pressure and upper airway tissue reconstructive surgery for OSA treatment, novel therapies, such as intermittent hypoxia conditioning (controlled exposures to mild hypoxic episodes followed by periods of normoxia or hyperoxia) targeting circadian clock genes dysregulated by OSA, can be further developed and integrated for improving cardiovascular health, especially in populations with disrupted sleep patterns or heightened salt sensitivity.<\/jats:p>","DOI":"10.1042\/cs20258876","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:03:17Z","timestamp":1775818997000},"page":"639-650","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of circadian gene expression in the divergent effects of intermittent hypoxia and sleep fragmentation on blood pressure"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7506-7623","authenticated-orcid":false,"given":"Eileen","family":"Chen","sequence":"first","affiliation":[{"name":"1Virginia Commonwealth University School of Medicine (M.D. Class 2027), Richmond, VA 23298, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1681-639X","authenticated-orcid":false,"given":"Pearl\u00a0L.","family":"Yu","sequence":"additional","affiliation":[{"name":"2Division of Pediatric Pulmonology & Sleep Medicine, Department of Pediatrics, Virginia Commonwealth University, Richmond, VA 23298, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-3329","authenticated-orcid":false,"given":"Lei","family":"Xi","sequence":"additional","affiliation":[{"name":"3Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"2026041007031051300_B1","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/s41440-024-01622-w","article-title":"The WHO Global report 2023 on hypertension warning the emerging hypertension burden in globe and its treatment strategy","volume":"47","author":"Kario","year":"2024","journal-title":"Hypertens. 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