{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:52:44Z","timestamp":1792270364840,"version":"4.4.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid\u2010late pregnancy, it is urgent to further explore whether it affects the long\u2010term synthesis of NO in offspring vascular endothelial cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Pregnant Sprague\u2013Dawley rats were housed in a normoxic or hypoxic (10.5% O\n              <jats:sub>2<\/jats:sub>\n              ) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO\u2010dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine\u2010induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR\u2010155\u20105p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR\u2010155\u20105p\/NADPH oxidase 2\/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.032079","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T11:38:16Z","timestamp":1705664296000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR\u2010155\u20105p\/NADPH Oxidase\/Reactive Oxygen Species Axis in Male Offspring Vessels"],"prefix":"10.1161","volume":"13","author":[{"given":"Meng","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao University Jinan 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