{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:10:45Z","timestamp":1792761045172,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["5R01HL151613"],"award-info":[{"award-number":["5R01HL151613"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:p>\n                    Venous thromboembolism (VTE) is a leading cause of morbidity and mortality, with risk heightened in premenopausal women with obesity or use estrogen-based oral contraceptives. When both risk factors are present, the thrombosis risk increases substantially. Protein S (PS), an essential anticoagulant cofactor, is downregulated by both estrogen and obesity, but the molecular basis for this suppression remains poorly defined. We investigated the effect of estrogen and obesity on PS expression using plasma samples from 157 women stratified by BMI and contraceptive use, alongside 40 mice categorized as lean or obese with or without estrogen pellet treatment. The levels of PS were reduced by either estrogen or obesity alone, and the combined effect increased thrombin generation. In HepG2 hepatocytes, hypoxic conditions (1%\u201310% O\n                    <jats:sub>2<\/jats:sub>\n                    ) mimicking obesity, with or without 17 \u03b2-estradiol, suppressed\n                    <jats:italic>PROS1<\/jats:italic>\n                    transcription and promoter activity. ChIP confirmed direct binding of hypoxia-inducible factor 1\u03b1 (HIF1\u03b1) to the\n                    <jats:italic>PROS1<\/jats:italic>\n                    promoter, repressing gene expression. These findings define a mechanistic pathway through which estrogen and obesity converge to suppress PS synthesis, providing insight into the elevated thrombosis risk observed in women with obesity using estrogen-based contraceptives.\n                  <\/jats:p>","DOI":"10.1172\/jci193976","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T19:00:52Z","timestamp":1763319652000},"source":"Crossref","is-referenced-by-count":4,"title":["Estrogen and obesity synergistically suppress protein S via HIF1\u03b1, enhancing thrombosis potential"],"prefix":"10.1172","volume":"135","author":[{"given":"Mohammad A.","family":"Mohammad","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narender","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary 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