{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:07:05Z","timestamp":1790798825887,"version":"4.1.0"},"reference-count":99,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["P20GM104357"],"award-info":[{"award-number":["P20GM104357"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["K99HL130577"],"award-info":[{"award-number":["K99HL130577"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:p> Preeclampsia (PE), a hypertensive disorder of pregnancy, is increasing as a major contributor to perinatal and long-term morbidity of mother and offspring. PE is thought to originate from ischemic insults in the placenta driving the release of prohypertensive anti-angiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1)] and proinflammatory [tumor necrosis factor-\u03b1 (TNF-\u03b1)] factors into the maternal circulation. Whereas the increased incidence of PE is hypothesized to be largely due to the obesity pandemic, the mechanisms whereby obesity increases this risk are unknown. The maternal endothelium is targeted by placental and adipose tissue-derived factors like sFlt-1 and TNF-\u03b1 that promote hypertension during pregnancy, resulting in vascular dysfunction and hypertension. Interestingly, not all obese pregnant women develop PE. Data suggest that obese pregnant women with the greatest metabolic abnormalities have the highest incidence of PE. Identifying obesity-related mechanisms driving hypertension in some obese pregnant women and pathways that protect normotensive obese pregnant women, may uncover novel protocols to treat PE. Metabolic abnormalities, such as increased circulating leptin, glucose, insulin, and lipids, are likely to increase the risk for PE in obese women. It is not only important to understand whether each of these metabolic factors contribute to the increased risk for PE in obesity, but also their cumulative effects. This is particularly relevant to obese pregnant women with gestational diabetes mellitus (GDM) where all of these factors are increased and the risk for PE is highest. It is speculated that these factors potentiate the anti-angiogenic and proinflammatory mechanisms of placental ischemia-induced vascular dysfunction thereby contributing to the increasing incidence of PE. <\/jats:p>","DOI":"10.1152\/ajpregu.00440.2016","type":"journal-article","created":{"date-parts":[[2016,11,30]],"date-time":"2016-11-30T22:30:38Z","timestamp":1480545038000},"page":"R5-R12","source":"Crossref","is-referenced-by-count":103,"title":["Metabolic abnormalities and obesity\u2019s impact on the risk for developing preeclampsia"],"prefix":"10.1152","volume":"312","author":[{"given":"Frank T.","family":"Spradley","sequence":"first","affiliation":[{"name":"Department of Surgery, Department of Physiology and Biophysics, Cardiovascular-Renal Research Center, Women\u2019s Health Research Center, The University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.114.124677"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1177\/2042018815577039"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000437382.03963.88"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2012.705395"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515484112"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.09.002"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.09.018"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1790"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.04.033"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2007.12.010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.06.001"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-2559a"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(89)90900-9"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1514"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/10641955.2013.837175"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000564"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/pd.4519"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2007.00489.x"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.4.H1317"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15196.x"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.11.024"},{"key":"B22","first-page":"450","volume":"24","author":"Easmin S","year":"2015","journal-title":"Mymensingh Med J"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00298"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.06.007"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.06.006"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-1332"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2012.12.006"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2016.02.007"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.821181"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-015-9491-2"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2014.36"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.02.024"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.112623"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.01.001"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1272"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s10995-011-0741-9"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13156"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3371-0"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.08.004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1968.tb02915.x"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1053\/meta.2000.6750"},{"key":"B42","first-page":"101","volume":"36","author":"Jarmuzek P","year":"2015","journal-title":"Neuro Endocrinol Lett"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303445"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.117259"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-319749"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.670"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.03.007"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3386-6"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.12.006"},{"key":"B50","first-page":"650","volume":"6","author":"Li HP","year":"2013","journal-title":"Int J Clin Exp Pathol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12164"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2012.44.4.021"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082310"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000003732"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2015.1094792"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2004.00337.x"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1159\/000329821"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13257"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.001133"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2590"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00167.2012"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2772-4"},{"key":"B63","first-page":"171","volume":"66","author":"Masuyama H","year":"2012","journal-title":"Acta Med Okayama"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2009.101"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2009.085"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c3428"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1570027"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/S1701-2163(15)30786-6"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00286.2014"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.57"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4035-z"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4035-z"},{"key":"B73","first-page":"477","volume":"41","author":"Popova P","year":"2016","journal-title":"Minerva Endocrinol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2672"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.191213"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2013-000010"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1097\/OGX.0b013e3182331028"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.12.008"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/uog.6126"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1177\/1933719109348252"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12506"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2015.08.002"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1177\/1933719114557899"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1997.272.2.R441"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00178.2015"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.157743"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3678"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509819"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2016.03.001"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000124460.67539.1d"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1002\/uog.14811"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00049.2012"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.00588"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-254219"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.02.001"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21412"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-11-57"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.03.020"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.08.006"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00440.2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T02:06:08Z","timestamp":1567994768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00440.2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,1]]},"references-count":99,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1,1]]}},"alternative-id":["10.1152\/ajpregu.00440.2016"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00440.2016","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,1]]}}}