Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3390/ijms22020564 http://hdl.handle.net/11449/209959 |
Resumo: | Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT (TM) PicoGreen(R) dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70-85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP. |
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Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomesadverse maternal-fetal outcomesbiomarkerscell-free DNAgestational hypertensionpreeclampsiaPrevious studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT (TM) PicoGreen(R) dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70-85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)American Heart AssociationNational Institutes of Health (NIH)Univ Mississippi, Med Ctr, Sch Med, Dept Pharmacol & Toxicol, Jackson, MS 39216 USAUniv Estadual Paulista, Inst Biosci, Dept Biophys & Pharmacol, BR-18618689 Botucatu, SP, BrazilUniv Mississippi, Med Ctr, Sch Med, Dept Surg, Jackson, MS 39216 USAUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, BR-14049900 Ribeirao Preto, SP, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP, BrazilUniv Estadual Paulista, Inst Biosci, Dept Biophys & Pharmacol, BR-18618689 Botucatu, SP, BrazilFAPESP: 06/50705-7FAPESP: 06/58157-9FAPESP: 06/58389-7American Heart Association: 19CDA34670055FAPESP: 19/07230-8National Institutes of Health (NIH): K08GM138812-01National Institutes of Health (NIH): R00HL130577National Institutes of Health (NIH): P20GM121334MdpiUniv MississippiUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Amaral, Lorena M.Sandrim, Valeria C. [UNESP]Kutcher, Matthew E.Spradley, Frank T.Cavalli, Ricardo C.Tanus-Santos, Jose E.Palei, Ana C.2021-06-25T12:34:52Z2021-06-25T12:34:52Z2021-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article16http://dx.doi.org/10.3390/ijms22020564International Journal Of Molecular Sciences. Basel: Mdpi, v. 22, n. 2, 16 p., 2021.http://hdl.handle.net/11449/20995910.3390/ijms22020564WOS:000611331600001Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal Of Molecular Sciencesinfo:eu-repo/semantics/openAccess2021-10-23T19:50:12Zoai:repositorio.unesp.br:11449/209959Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:34:26.355685Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
title |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
spellingShingle |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes Amaral, Lorena M. adverse maternal-fetal outcomes biomarkers cell-free DNA gestational hypertension preeclampsia |
title_short |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
title_full |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
title_fullStr |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
title_full_unstemmed |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
title_sort |
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes |
author |
Amaral, Lorena M. |
author_facet |
Amaral, Lorena M. Sandrim, Valeria C. [UNESP] Kutcher, Matthew E. Spradley, Frank T. Cavalli, Ricardo C. Tanus-Santos, Jose E. Palei, Ana C. |
author_role |
author |
author2 |
Sandrim, Valeria C. [UNESP] Kutcher, Matthew E. Spradley, Frank T. Cavalli, Ricardo C. Tanus-Santos, Jose E. Palei, Ana C. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Mississippi Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Amaral, Lorena M. Sandrim, Valeria C. [UNESP] Kutcher, Matthew E. Spradley, Frank T. Cavalli, Ricardo C. Tanus-Santos, Jose E. Palei, Ana C. |
dc.subject.por.fl_str_mv |
adverse maternal-fetal outcomes biomarkers cell-free DNA gestational hypertension preeclampsia |
topic |
adverse maternal-fetal outcomes biomarkers cell-free DNA gestational hypertension preeclampsia |
description |
Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT (TM) PicoGreen(R) dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70-85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T12:34:52Z 2021-06-25T12:34:52Z 2021-01-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3390/ijms22020564 International Journal Of Molecular Sciences. Basel: Mdpi, v. 22, n. 2, 16 p., 2021. http://hdl.handle.net/11449/209959 10.3390/ijms22020564 WOS:000611331600001 |
url |
http://dx.doi.org/10.3390/ijms22020564 http://hdl.handle.net/11449/209959 |
identifier_str_mv |
International Journal Of Molecular Sciences. Basel: Mdpi, v. 22, n. 2, 16 p., 2021. 10.3390/ijms22020564 WOS:000611331600001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal Of Molecular Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
16 |
dc.publisher.none.fl_str_mv |
Mdpi |
publisher.none.fl_str_mv |
Mdpi |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129439442141184 |