Significance of angiogenic factors imbalance in preeclampsia

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The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt-1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstratedin multiple clinical and experimental studies. These studies are complemented by animal studies,...

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Autor: Mateus, Julio
Formato: artículo
Fecha de Publicación:2015
Institución:Sociedad Peruana de Obstetricia y Ginecología
Repositorio:Revista Peruana de Ginecología y Obstetricia
Lenguaje:español
OAI Identifier:oai:ojs.pkp.sfu.ca:article/157
Enlace del recurso:http://51.222.106.123/index.php/RPGO/article/view/157
Nivel de acceso:acceso abierto
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dc.title.none.fl_str_mv Significance of angiogenic factors imbalance in preeclampsia
Significancia del desbalance de los factores angiogénicos en preeclampsia
title Significance of angiogenic factors imbalance in preeclampsia
spellingShingle Significance of angiogenic factors imbalance in preeclampsia
Mateus, Julio
title_short Significance of angiogenic factors imbalance in preeclampsia
title_full Significance of angiogenic factors imbalance in preeclampsia
title_fullStr Significance of angiogenic factors imbalance in preeclampsia
title_full_unstemmed Significance of angiogenic factors imbalance in preeclampsia
title_sort Significance of angiogenic factors imbalance in preeclampsia
dc.creator.none.fl_str_mv Mateus, Julio
author Mateus, Julio
author_facet Mateus, Julio
author_role author
description The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt-1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstratedin multiple clinical and experimental studies. These studies are complemented by animal studies, inwhich overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although,the origin of this disease remains unknown, genetic, environmental, and immunological factorsappear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibitthe proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growthfactor (PlGF), affecting the normal vascular development in the placenta and the physiological vascularadaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctionalplacenta, are released into the maternal circulation and elevated circulating concentrationsof these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease.Multiple studies have reported the capacity of circulating antiangiogenic factor concentrationsto predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1and sEng are inconsistent across these studies and therefore their clinical use in this population is notrecommended. On the other hand, maternal plasma concentrations of these factors appear to havea better performance in women with symptoms of PE. Among the possible combinations, the ratiosof sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnosePE as well as the highest predictive values for PE-related adverse outcomes. These propertiessupport their clinical use in this setting and it is likely those ancillary tests will be incorporated to theclinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis ofPE, also have stimulated investigation of new targeted therapies. The biological and pharmacokineticproperties of statins have converted them in one of the most promising preventive therapies forthis disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors.In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, andplacental transference of these therapies.Keywords: Angiogenic factors, preeclampsia, placenta growth factor, endothelial vascular growth factor,endoglin, soluble fms-like tyrosine kinase-
publishDate 2015
dc.date.none.fl_str_mv 2015-01-28
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dc.identifier.none.fl_str_mv http://51.222.106.123/index.php/RPGO/article/view/157
url http://51.222.106.123/index.php/RPGO/article/view/157
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language spa
dc.relation.none.fl_str_mv http://51.222.106.123/index.php/RPGO/article/view/157/139
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dc.publisher.none.fl_str_mv Sociedad Peruana de Obstetricia y Ginecología
publisher.none.fl_str_mv Sociedad Peruana de Obstetricia y Ginecología
dc.source.none.fl_str_mv The Peruvian Journal of Gynecology and Obstetrics ; Vol. 60 No. 4 (2014); 333-343
Revista Peruana de Ginecología y Obstetricia; Vol. 60 Núm. 4 (2014); 333-343
2304-5132
2304-5124
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spelling Significance of angiogenic factors imbalance in preeclampsiaSignificancia del desbalance de los factores angiogénicos en preeclampsiaMateus, JulioThe role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt-1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstratedin multiple clinical and experimental studies. These studies are complemented by animal studies, inwhich overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although,the origin of this disease remains unknown, genetic, environmental, and immunological factorsappear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibitthe proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growthfactor (PlGF), affecting the normal vascular development in the placenta and the physiological vascularadaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctionalplacenta, are released into the maternal circulation and elevated circulating concentrationsof these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease.Multiple studies have reported the capacity of circulating antiangiogenic factor concentrationsto predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1and sEng are inconsistent across these studies and therefore their clinical use in this population is notrecommended. On the other hand, maternal plasma concentrations of these factors appear to havea better performance in women with symptoms of PE. Among the possible combinations, the ratiosof sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnosePE as well as the highest predictive values for PE-related adverse outcomes. These propertiessupport their clinical use in this setting and it is likely those ancillary tests will be incorporated to theclinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis ofPE, also have stimulated investigation of new targeted therapies. The biological and pharmacokineticproperties of statins have converted them in one of the most promising preventive therapies forthis disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors.In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, andplacental transference of these therapies.Keywords: Angiogenic factors, preeclampsia, placenta growth factor, endothelial vascular growth factor,endoglin, soluble fms-like tyrosine kinase-La participación de los factores antiangiogénicos, la forma soluble de la fms-semejante a la tirosinaquinasa (Flt-1s) y la endoglina soluble (Engs), en el desarrollo de la preeclampsia (PE) se ha demostradoen múltiples estudios clínicos y experimentales. Estos estudios están complementados porestudios en animales, en los cuales la sobreexpresión de estos factores antiangiogénicos originamanifestaciones clínicas muy similares a la PE. El origen de esta enfermedad permanece desconocido.Sin embargo, factores genéticos, ambientales e inmunológicos parecen alterar el desarrollonormal de la placenta, lo cual conduce últimamente a la PE. Flt-1s y Engs inhiben la producción ylas propiedades proangiogénicas del factor de crecimiento vascular endotelial (FCVE) y del factorde crecimiento placentario (FCP), necesarios para el desarrollo normal vascular de la placenta y lasadaptaciones vasculares fisiológicas del embarazo. Cantidades exageradas de Flt-1s y Engs se producenen la placenta disfuncional y se liberan en la circulación materna. Altas concentraciones deFlt-1s y Engs se encuentran en la circulación materna semanas antes de que la enfermedad sea detectadaclínicamente. Las capacidades de los factores angiogénicos para predecir PE en embarazosasintomáticos de riesgo bajo y alto son inconsistentes y no útiles para el uso clínico. Por otro lado,proporciones de los factores Flt-1s/FCP, FCP/Flt-1s, y FCP/Eng poseen valores predictivos más altospara diagnosticar PE y predecir sus complicaciones en mujeres con sintomatología de PE. En estascondiciones, el uso clínico de estos marcadores biológicos podría ser implementado en un futurocercano. Las propiedades biológicas y farmacocinéticas de las estatinas las convierten en uno delos medicamentos con más potencial preventivo para la PE. Otros opciones terapéuticas que seestán estudiando son medicamentos que directamente inhiban los factores antiangiogénicos circulantes.Estudios in vitro y estudios pilotos clínicos se están realizando actualmente examinandola seguridad materno-fetal, la transferencia placentaria y la efectividad de estas terapias.Palabras clave: Factores angiogénicos, preeclampsia, factor de crecimiento placentario, factor decrecimiento vascular endotelial, endoglina, forma soluble de la fms-semejante a la tirosina quinasa.Sociedad Peruana de Obstetricia y Ginecología2015-01-28info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://51.222.106.123/index.php/RPGO/article/view/157The Peruvian Journal of Gynecology and Obstetrics ; Vol. 60 No. 4 (2014); 333-343Revista Peruana de Ginecología y Obstetricia; Vol. 60 Núm. 4 (2014); 333-3432304-51322304-5124reponame:Revista Peruana de Ginecología y Obstetriciainstname:Sociedad Peruana de Obstetricia y Ginecologíainstacron:SPOGspahttp://51.222.106.123/index.php/RPGO/article/view/157/139info:eu-repo/semantics/openAccessoai:ojs.pkp.sfu.ca:article/1572015-01-28T22:23:54Z
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