{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:43:33Z","timestamp":1789616613456,"version":"build-2803163510"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior , Brasil","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study investigated whether soluble fms-like tyrosine kinase-1 (sFlt-1) and angiotensin II type 1 receptor autoantibodies (AT1-AA) \u2013 key mediators of preeclampsia (PE) pathophysiology \u2013 remain elevated ten years postpartum, thereby contributing to the long-term cardiovascular disease (CVD) risk in women with a history of PE. In a retrospective cohort nested within the PERLA-Brazil project, 205 women were enrolled: 103 with a documented history of PE (PH group) and 102 with normotensive pregnancies (NH group). Participants completed standardized interviews, underwent physical evaluations, and provided blood samples for sFlt-1 and AT1-AA quantification by enzyme-linked immunosorbent assay (ELISA), alongside comprehensive clinical and demographic data collection. No significant differences were observed in circulating sFlt-1 (90.25\u2009\u00b1\u20096.11 pg\/mL in PH vs. 93.30\u2009\u00b1\u20095.54 pg\/mL in NH, p\u2009=\u20090.886) or AT1-AA levels (6.80\u2009\u00b1\u20090.16 ng\/mL in PH vs. 6.34\u2009\u00b1\u20090.18 ng\/mL in NH, p\u2009=\u20090.060) between groups a decade after the index pregnancy. Clinical and biochemical data were collected and compared between groups, with multivariable models adjusted for age, body mass index, and educational attainment. As results, it was observed that women with severe PE history had higher systolic and diastolic blood pressure, higher low-density lipoprotein cholesterol, and a greater prevalence of hypertension. These findings suggest that the long-term cardiovascular burden after PE is not explained by increased plasma levels of sFlt-1 or AT1-AA, but may instead reflect durable downstream vascular and metabolic remodeling. The study underscores PE as a marker of future cardiovascular vulnerability and highlights the need to identify additional mechanisms and biomarkers underlying this risk.This highlights PE as an early-life stressor with persistent effects and underscores the need of lifelong CVD prevention strategies for affected women, as well as the importance of identifying additional biological or physiological markers associated with their sustained risk.<\/jats:p>","DOI":"10.1038\/s41598-026-50409-1","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:37:01Z","timestamp":1778060221000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating levels of sFlt-1 and AT1-AA in women with prior preeclampsia: a 10-year postpartum cross-sectional analysis (PERLA-Brazil study)"],"prefix":"10.1038","volume":"16","author":[{"given":"Tha\u00edse Emilia Moreira","family":"da Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Macedo","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Silva","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thays Santos","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Oliveira","family":"Perucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano Armstrong","family":"Arnosti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luci Maria Sant\u2019Ana","family":"Dusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara","family":"Mayrink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Nessralla","family":"Alpoim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"issue":"6","key":"50409_CR1","doi-asserted-by":"publisher","first-page":"e237","DOI":"10.1097\/AOG.0000000000003891","volume":"135","author":"Gestational Hypertension and Preeclampsia","year":"2020","unstructured":"Gestational Hypertension and Preeclampsia. ACOG Practice Bulletin, Number 222. Obstet. Gynecol. 135 (6), e237\u2013e60 (2020).","journal-title":"Obstet. Gynecol."},{"issue":"3","key":"50409_CR2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1161\/01.HYP.0000256565.20983.d4","volume":"49","author":"CA Hubel","year":"2007","unstructured":"Hubel, C. A. et al. Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension 49 (3), 612\u2013617 (2007).","journal-title":"Hypertension"},{"issue":"4","key":"50409_CR3","doi-asserted-by":"publisher","first-page":"224","DOI":"10.7326\/M17-2740","volume":"169","author":"JJ Stuart","year":"2018","unstructured":"Stuart, J. J. et al. Hypertensive disorders of pregnancy and maternal cardiovascular disease risk factor development: An observational cohort study. Ann. Intern. Med. 169(4), 224\u201332 (2018).","journal-title":"Ann. Intern. Med."},{"issue":"7627","key":"50409_CR4","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1136\/bmj.39335.385301.BE","volume":"335","author":"L Bellamy","year":"2007","unstructured":"Bellamy, L., Casas, J. P., Hingorani, A. D. & Williams, D. J. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: Systematic review and meta-analysis. BMJ 335(7627), 974 (2007).","journal-title":"BMJ"},{"issue":"4","key":"50409_CR5","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1161\/HYPERTENSIONAHA.107.097790","volume":"51","author":"CC Zhou","year":"2008","unstructured":"Zhou, C. C. et al. Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin\/nuclear factor of activated T-cells signaling. Hypertension 51 (4), 1010\u20131019 (2008).","journal-title":"Hypertension"},{"issue":"6","key":"50409_CR6","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1161\/CIRCRESAHA.122.321228","volume":"132","author":"LA Biwer","year":"2023","unstructured":"Biwer, L. A. et al. Smooth muscle mineralocorticoid receptor promotes hypertension after preeclampsia. Circ. Res. 132(6), 674\u201389 (2023).","journal-title":"Circ. Res."},{"issue":"9","key":"50409_CR7","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1161\/01.RES.0000147365.86159.f5","volume":"95","author":"S Ahmad","year":"2004","unstructured":"Ahmad, S. & Ahmed, A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ. Res. 95 (9), 884\u2013891 (2004).","journal-title":"Circ. Res."},{"key":"50409_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58091196","author":"AF Tataru-Copos","year":"2022","unstructured":"Tataru-Copos, A. F., Popescu, M. I., Murvai, R. & El Kharoubi, A. Efficiency of sFlt-1\/PlGF ratio in preeclampsia diagnosis. Medicina (Kaunas) https:\/\/doi.org\/10.3390\/medicina58091196 (2022).","journal-title":"Medicina (Kaunas)"},{"issue":"3","key":"50409_CR9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1095\/biolreprod.114.126227","volume":"93","author":"Z Jiang","year":"2015","unstructured":"Jiang, Z. et al. A Role of sFlt-1 in Oxidative Stress and Apoptosis in Human and Mouse Pre-Eclamptic Trophoblasts. Biol. Reprod. 93 (3), 73 (2015).","journal-title":"Biol. Reprod."},{"issue":"4","key":"50409_CR10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/aji.12072","volume":"69","author":"F Herse","year":"2013","unstructured":"Herse, F. & LaMarca, B. Angiotensin II type 1 receptor autoantibody (AT1-AA)-mediated pregnancy hypertension. Am. J. Reprod. Immunol. 69(4), 413\u20138 (2013).","journal-title":"Am. J. Reprod. Immunol."},{"issue":"5","key":"50409_CR11","doi-asserted-by":"publisher","first-page":"e75","DOI":"10.1161\/HYP.0000000000000227","volume":"80","author":"BT Alexander","year":"2023","unstructured":"Alexander, B. T. et al. Appraising the preclinical evidence of the role of the Renin-Angiotensin-Aldosterone System in antenatal programming of maternal and offspring cardiovascular health across the life course: Moving the field forward: A scientific statement from the American Heart Association. Hypertension 80(5), e75\u2013e89 (2023).","journal-title":"Hypertension"},{"issue":"2","key":"50409_CR12","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1161\/HYPERTENSIONAHA.111.00157","volume":"61","author":"AH Siddiqui","year":"2013","unstructured":"Siddiqui, A. H. et al. Angiotensin receptor agonistic autoantibody-mediated soluble fms-like tyrosine kinase-1 induction contributes to impaired adrenal vasculature and decreased aldosterone production in preeclampsia. Hypertension 61 (2), 472\u2013479 (2013).","journal-title":"Hypertension"},{"key":"50409_CR13","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.cca.2012.10.006","volume":"415","author":"LM Dusse","year":"2013","unstructured":"Dusse, L. M. et al. Is there a link between endothelial dysfunction, coagulation activation and nitric oxide synthesis in preeclampsia?. Clin. Chim. Acta 415, 226\u20139 (2013).","journal-title":"Clin. Chim. Acta"},{"issue":"23\u201324","key":"50409_CR14","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.cca.2011.07.030","volume":"412","author":"PN Alpoim","year":"2011","unstructured":"Alpoim, P. N. et al. ADAMTS13, FVIII, von Willebrand factor, ABO blood group assessment in preeclampsia. Clin. Chim. Acta 412(23\u201324), 2162\u20136 (2011).","journal-title":"Clin. Chim. Acta"},{"key":"50409_CR15","first-page":"i","volume":"894","author":"Obesity","year":"2000","unstructured":"Obesity. preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 894, i\u2013xii (2000).","journal-title":"World Health Organ. Tech. Rep. Ser."},{"issue":"2","key":"50409_CR16","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1161\/HYPERTENSIONAHA.122.19482","volume":"80","author":"F Gaccioli","year":"2023","unstructured":"Gaccioli, F. et al. Increased placental sFLT1 (soluble fms-like tyrosine kinase receptor-1) drives the antiangiogenic profile of maternal serum preceding preeclampsia but not fetal growth restriction. Hypertension 80(2), 325\u2013334 (2023).","journal-title":"Hypertension"},{"issue":"7","key":"50409_CR17","doi-asserted-by":"publisher","first-page":"11495","DOI":"10.3390\/ijms150711495","volume":"15","author":"HP Wang","year":"2014","unstructured":"Wang, H. P. et al. Exposure to AT1 receptor autoantibodies during pregnancy increases susceptibility of the maternal heart to postpartum ischemia-reperfusion injury in rats. Int. J. Mol. Sci. 15(7), 11495\u2013509 (2014).","journal-title":"Int. J. Mol. Sci."},{"issue":"22","key":"50409_CR18","doi-asserted-by":"publisher","first-page":"2743","DOI":"10.1016\/j.jacc.2019.09.052","volume":"74","author":"MC Honigberg","year":"2019","unstructured":"Honigberg, M. C. et al. Long-term cardiovascular risk in women with hypertension during pregnancy. J. Am. Coll. Cardiol. 74(22), 2743\u201354 (2019).","journal-title":"J. Am. Coll. Cardiol."},{"issue":"18","key":"50409_CR19","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1016\/j.jacc.2020.03.028","volume":"75","author":"VD Garovic","year":"2020","unstructured":"Garovic, V. D. et al. Incidence and long-term outcomes of hypertensive disorders of pregnancy. J. Am. Coll. Cardiol. 75(18), 2323\u201334 (2020).","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50409-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50409-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50409-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:28:42Z","timestamp":1783380522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-50409-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,6]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["50409"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-50409-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,6]]},"assertion":[{"value":"2 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Research Ethics Committee at UFMG (CAAE: 4887721.0.0000.5149) and by the Julia Kubitschek Hospital (Belo Horizonte, Brazil) (CAAE:46792921.3.3002.5119). All procedures were conducted with the principles of the Declaration of Helsinki. Informed consent was obtained from all participants prior to their inclusion in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20845"}}