Prognostic value of anti- and proangiogenic factors in severe preeclampsia
Margarita Yu. Vasileva , Ilya V. Smirnov , Valentina V. Ishkaraeva , Natalya Yu. Yakovleva , Elena Yu. Vasilyeva , Sergey V. Chepanov , Lyudmila V. Kalosha , Olga N. Tamakhina , Sergey A. Selkov , Irina E. Zazerskaya
Journal of obstetrics and women's diseases ›› 2023, Vol. 72 ›› Issue (2) : 5 -17.
Prognostic value of anti- and proangiogenic factors in severe preeclampsia
BACKGROUND: Over the years, preeclampsia has remained a common pathology of pregnancy. Its severe form poses a significant threat to the health of the woman and the fetus. To assess the risk of developing preeclampsia, biochemical screening for placental growth factor and soluble tyrosine kinase-1 is carried out. The soluble glycoprotein endoglin, which regulates angiogenesis by influencing cell activation, adhesion, and migration, can supplement the idea of the imbalance of vascular factors in severe preeclampsia. A holistic study of anti- and proangiogenic factors can significantly complement the diagnosis of preeclampsia at the preclinical stage and a look at the course and treatment of this pregnancy complication.
AIM: The aim of this work was to evaluate the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin, soluble tyrosine kinase-1, placental growth factor) and compare the obtained data with the clinical manifestations of severe preeclampsia.
MATERIALS AND METHODS: This case-control study included 81 pregnant women. The main group consisted of patients with severe preeclampsia (n = 41), while the control group comprised individuals with normal pregnancy (n = 40). To determine soluble glycoprotein endoglin levels in biological fluids, we used a new ELISA kit developed in the Laboratory of Hybridoma Technology, Academician A.M. Granov Russian Research Center for Radiology and Surgical Technologies (Saint Petersburg, Russia). placental growth factor and soluble tyrosine kinase-1 concentrations were assessed by electrochemiluminescence immunoassay using commercial Roche Diagnostics kits. Statistical analysis was performed using the StatTech v.3.0.6 program (Stattech Ltd., Russia).
RESULTS: When analyzing the concentrations of anti- and proangiogenic factors (soluble glycoprotein endoglin in the blood serum and urine, soluble tyrosine kinase-1, placental growth factor and the ratio of these factors), depending on the study group, statistically significant results were obtained (p < 0.05). The diagnostic significance of serum and urine soluble glycoprotein endoglin levels in predicting the probability of severe preeclampsia was assessed by the method of ROC curve analysis. Statistically significant differences (p < 0.05) were found in the analysis of the concentrations of anti- and pro-angiogenic factors depending on the clinical manifestations such as systolic blood pressure ≥ 160 mm Hg (except for placental growth factor level), a multiple increase in urine soluble glycoprotein endoglin level with massive proteinuria, an increase in soluble glycoprotein endoglin levels in biological fluids with an increase in edematous syndrome. Correlation analysis revealed a significant relationship between anti- and proangiogenic factors and the term of delivery, as well as urine soluble glycoprotein endoglin level and the duration of the treatment.
CONCLUSIONS: The data obtained complement the concept of severe preeclampsia. Knowing the concentrations of soluble glycoprotein endoglin in the blood serum and urine allows for predicting the timing of delivery and the possible duration of treatment, which is critical in the management of patients with severe preeclampsia.
severe preeclampsia / antiangiogenic factors / proangiogenic factors / soluble endoglin / soluble tyrosine kinase-1 / placental growth factor
| [1] |
Aleksandrova GA, Golubev NA, Tyurina EM, et al. Osnovnye pokazateli zdorov’ya materi i rebenka, deyatel’nost’ sluzhby ohrany detstva i rodovspomozheniya v Rossiiskoi Federatsii. Sbornik TsNIIOIZ. Moscow; 2019. (In Russ.) [cited 2023 Jan 3]. Available from: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/046/523/original/13_Osnovnye_pokazateli_zdorov’ya_materi_i_rebenka_deyatel’nost’_sluzhby_ohrany_detstva_i_rodovspomozheniya_2018.doc?1564572095 |
| [2] |
Александрова Г.А., Голубев Н.А., Тюрина Е.М. и др. Основные показатели здоровья матери и ребенка, деятельность службы охраны детства и родовспоможения в Российской Федерации. Сборник ЦНИИОИЗ. Москва. 2019 [дата обращения 03.01.2023]. Доступ по ссылке: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/046/523/original/13_Основные_показатели_здоровья_матери_и_ребенка_деятельность_службы_охраны_детства_и_родовспоможения_ 2018.doc?1564572095 |
| [3] |
Rana S, Burke SD, Karumanchi SA. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders. Am J Obstet Gynecol. 2022;226(2S):S1019–S1034. DOI: 10.1016/j.ajog.2020.10.022 |
| [4] |
Rana S., Burke S.D., Karumanchi S.A. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders // Am. J. Obstet. Gynecol. 2022. Vol. 226. No. 2S. P. S1019–S1034. DOI: 10.1016/j.ajog.2020.10.022 |
| [5] |
Kuo CY, Guo T, Cabrera-Luque J, et al. Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three-dimensional bioprinted placenta model. J Biomed Mater Res A. 2018;106(6):1476–1487. DOI: 10.1002/jbm.a.36350 |
| [6] |
Kuo C.Y., Guo T., Cabrera-Luque J., et al. Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three-dimensional bioprinted placenta model // J. Biomed. Mater. Res. A. 2018. Vol. 106. No. 6. P. 1476–1487. DOI: 10.1002/jbm.a.36350 |
| [7] |
Rana S, Lemoine E, Granger JP, et al. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. Lippincott Williams and Wilkins. 2019;124(7):1094–1112. DOI: 10.1161/circresaha.118.313276 |
| [8] |
Rana S., Lemoine E., Granger J.P., et al. Preeclampsia: pathophysiology, challenges, and perspectives // Circ. Res. Lippincott Williams and Wilkins. 2019. Vol. 124. No. 7. P. 1094–1112. DOI: 10.1161/circresaha.118.313276 |
| [9] |
Tarca AL, Romero R, Benshalom-Tirosh N, et al. The prediction of early preeclampsia: Results from a longitudinal proteomics study. PLoS One. 2019;14(6). DOI: 10.1371/journal.pone.0217273 |
| [10] |
Tarca A.L., Romero R., Benshalom-Tirosh N., et al. The prediction of early preeclampsia: results from a longitudinal proteomics study // PLoS One. 2019. Vol. 14. No. 6. DOI: 10.1371/journal.pone.0217273 |
| [11] |
O’Gorman N, Wright D, Poon LC, et al. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11–13 weeks’ gestation. Ultrasound Obstet Gynecol. 2017;49(6):751–755. DOI: 10.1002/uog.17399 |
| [12] |
O’Gorman N., Wright D., Poon L.C., et al. Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation // Ultrasound Obstet. Gynecol. 2017. Vol. 49. No. 6. P. 751–755. DOI: 10.1002/uog.17399 |
| [13] |
Duhig KE, Myers J, Seed PT, et al.; PARROT trial group. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial. Lancet. 2019;393(10183):1807–1818. DOI: 10.1097/01.aoa.0000652908.62221.48 |
| [14] |
Duhig K.E., Myers J., Seed P.T., et al.; PARROT trial group. Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial // Lancet. 2019. Vol. 393. No. 10183. P. 1807–1818. DOI: 10.1097/01.aoa.0000652908.62221.48 |
| [15] |
Smirnov IV, Gryazeva IV, Vasileva MY, et al. New highly sensitive sandwich ELISA system for soluble endoglin quantification in different biological fluids. Scand J Clin Lab Invest. 2018;78(6):515–523. DOI: 10.1080/00365513.2018.1516892 |
| [16] |
Smirnov I.V., Gryazeva I.V., Vasileva M.Y., et al. New highly sensitive sandwich ELISA system for soluble endoglin quantification in different biological fluids // Scand. J. Clin. Lab. Invest. 2018. Vol. 78. No. 6. P. 515–523. DOI: 10.1080/00365513.2018.1516892 |
| [17] |
Nogueira Reis ZS, Pereira JB, Costa LAC, et al. Soluble endoglin in urine as an early-pregnancy preeclampsia marker: antenatal longitudinal feasibility study. J Obstet Gynaecol. 2021;41(5):693–698. DOI: 10.1080/01443615.2020.1789851 |
| [18] |
Nogueira Reis Z.S., Pereira J.B., Costa L.A.C., et al. Soluble endoglin in urine as an early-pregnancy preeclampsia marker: antenatal longitudinal feasibility study // J. Obstet. Gynecol. 2021. Vol. 41. No. 5. P. 693–698. DOI: 10.1080/01443615.2020.1789851 |
| [19] |
Wu P, Haththotuwa R, Kwok CS, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2). DOI: 10.1161/CIRCOUTCOMES.116.003497 |
| [20] |
Wu P., Haththotuwa R., Kwok C.S., et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis // Circ. Cardiovasc. Qual. Outcomes. 2017. Vol. 10. No. 2. DOI: 10.1161/circoutcomes.116.003497 |
| [21] |
Verlohren S, Brennecke SP, Galindo A, et al. Clinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia. Pregnancy Hypertens. 2022;27:42–50. DOI: 10.1016/j.preghy.2021.12.003 |
| [22] |
Verlohren S., Brennecke S.P., Galindo A., et al. Clinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia // Pregnancy Hypertens. 2022. Vol. 27. P. 42–50. DOI: 10.1016/j.preghy.2021.12.003 |
| [23] |
Bettikher OA, Zazerskaya IE, Popova PV, et al. Preeclampsia features in pregnancy with gestational diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2019;68(5):19–36. (In Russ.) DOI: 10.17816/jowd68519-36 |
| [24] |
Беттихер О.А., Зазерская И.Е., Попова П.В., и др. Характеристика преэклампсии у беременных с гестационным диабетом // Журнал акушерства и женских болезней. 2019. Т. 68. № 5. С. 19–36. DOI: 10.17816/jowd68519-36 |
| [25] |
Kapustin R.V. Possibilities for prediction and prevention of preeclampsia in women with diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2018;67(3):20–29. (In Russ.) DOI: 10.17816/JOWD67320-29 |
| [26] |
Капустин Р.В. Возможности прогнозирования и профилактики преэклампсии у беременных с сахарным диабетом // Журнал акушерства и женских болезней. 2018. Т. 67. № 3. С. 20–29. DOI: 10.17816/JOWD67320-29 |
| [27] |
Levine RJ, Lam C, Qian C, et al.; CPEP Study Group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005. DOI: 10.1097/01.ogx.0000253489.32189.4d |
| [28] |
Levine R.J., Lam C., Qian C., et al.; CPEP Study Group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia // N. Engl. J. Med. 2006. Vol. 355. No. 10. P. 992–1005. DOI: 10.1097/01.ogx.0000253489.32189.4d |
| [29] |
Vasileva MY, Zazerskaya IE, Sel’kov SA, et al. Comparative analysis of methods for determining endoglin in the diagnosis of preeclampsia. Women’s health and reproduction: online publication. 2021;3(50). (In Russ.) [cited 2023 Jan 3]. Available from: https://whfordoctors.su/statyi/sravnitelnyj-analiz-metodik-opredelenija-jendoglina-v-diagnostike-prejeklampsii/ |
| [30] |
Васильева М.Ю., Зазерская И.Е., Сельков С.А., и др. Сравнительный анализ методик определения эндоглина в диагностике преэклампсии // Женское здоровье и репродукция: сетевое издание. 2021. Т. 3. № 50 [дата обращения: 03.01.2023]. Доступ по ссылке: https://whfordoctors.su/statyi/sravnitelnyj-analiz-metodik-opredelenija-jendoglina-v-diagnostike-prejeklampsii |
| [31] |
Binder J, Kalafat E, Palmrich P, et al. Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension. Am J Obstet Gynecol. 2021;225(3):305.e1–305.e14. DOI: 10.1016/j.ajog.2021.03.041 |
| [32] |
Binder J., Kalafat E., Palmrich P., et al. Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension // Am. J. Obstet. Gynecol. 2021. Vol. 225. No. 3. P. 305.e1–305.e14. DOI: 10.1016/j.ajog.2021.03.041 |
| [33] |
Perry H, Binder J, Kalafat E, et al. Angiogenic marker prognostic models in pregnant women with hypertension. Hypertension. 2020;75(3):755–761. DOI: 10.1161/hypertensionaha.119.13997 |
| [34] |
Perry H., Binder J., Kalafat E., et al. Angiogenic marker prognostic models in pregnant women with hypertension // Hypertension. 2020. Vol. 75. No. 3. P. 755–761. DOI: 10.1161/hypertensionaha.119.13997 |
| [35] |
National Institute for Health and Care Excellence (NICE). Hypertension in pregnancy: diagnosis and management. 2019 [cited 2023 Jan 3]. Available from: https://www.nice.org.uk/guidance/ng133/resources/hypertension-in-pregnancy-diagnosis-and-management-pdf-66141717671365 |
| [36] |
National Institute for Health and Care Excellence (NICE). Hypertension in pregnancy: diagnosis and management. 2019 [дата обращения: 03.01.2023]. Доступ по ссылке: https://www.nice.org.uk/guidance/ng133/resources/hypertension-in-pregnancy-diagnosis-and-management-pdf-66141717671365 |
| [37] |
Godzoyeva AO, Zazerskaya IE, Vasilyeva EYu, et al. Prognostic value of sFlt-1 and PlGF in the diagnosis of abnormally deep placental invasion. Journal of Obstetrics and Women’s Diseases. 2022;71(2):39–48. (In Russ.) DOI: 10.17816/JOWD88697 |
| [38] |
Годзоева А.О., Зазерская И.Е., Васильева Е.Ю., и др. Прогностическая значимость sflt-1 и plgf в диагностике глубокой инвазии плаценты // Журнал акушерства и женских болезней. 2022. Т. 71. № 2. С. 39–48. DOI: 10.17816/jowd88697 |
| [39] |
Iannaccone A, Reisch B, Mavarani L, et al. Soluble endoglin versus sFlt-1/PlGF ratio: detection of preeclampsia, HELLP syndrome, and FGR in a high-risk cohort. Hypertens Pregnancy. 2022;41(3–4):159–172. DOI: 10.1080/10641955.2022.2066119 |
| [40] |
Iannaccone A., Reisch B., Mavarani L., et al. Soluble endoglin versus sFlt-1/PlGF ratio: detection of preeclampsia, HELLP syndrome, and FGR in a high-risk cohort // Hypertens Pregnancy. 2022. Vol. 41. No. 3–4. P. 159–172. DOI: 10.1080/10641955.2022.2066119 |
| [41] |
Molina Pérez CJ, Nolasco Leaños AG, Carrillo Juárez RI, et al. Soluble endoglin and uterine artery flow Doppler ultrasonography as markers of progression to preeclampsia in women with gestational hypertension. Gynecol Obstet Invest. 2021;86(5):445–453. DOI: 10.1159/000519371 |
| [42] |
Molina Pérez C.J., Nolasco Leaños A.G., Carrillo Juárez R.I., et al. Soluble endoglin and uterine artery flow doppler ultrasonography as markers of progression to preeclampsia in women with gestational hypertension // Gynecol. Obstet. Invest. 2021. Vol. 86. No. 5. P. 445–453. DOI: 10.1159/000519371 |
| [43] |
Sun X, Su F, Chen X, et al. Doppler ultrasound and photoplethysmographic assessment for identifying pregnancy-induced hypertension. Exp Ther Med. 2020;19(3):1955–1960. DOI: 10.3892/etm.2019.8405 |
| [44] |
Sun X., Su F., Chen X., et al. Doppler ultrasound and photoplethysmographic assessment for identifying pregnancy-induced hypertension // Exp. Ther Med. 2020. Vol. 19. No. 3. P. 1955–1960. DOI: 10.3892/etm.2019.8405 |
| [45] |
Rodriguez-Fernandez JJ, Martinez-Garza LE, Sepulveda-Gonzalez G, et al. Serum biomarkers and Doppler pulsatile index increases likelihood ratio for prediction of preeclampsia in the second trimester of pregnancy. J Obstet Gynaecol. 2022;42(6):1722–1727. DOI: 10.1080/01443615.2022.2035331 |
| [46] |
Rodriguez-Fernandez J.J., Martinez-Garza L.E., Sepulveda-Gonzalez G., et al. Serum biomarkers and Doppler pulsatile index increases likelihood ratio for prediction of preeclampsia in the second trimester of pregnancy // J. Obstet. Gynaecol. 2022. Vol. 42. No. 6. P. 1722–1727. DOI: 10.1080/01443615.2022.2035331 |
| [47] |
Schmella MJ, Assibey-Mensah V, Parks WT, et al. Plasma concentrations of soluble endoglin in the maternal circulation are associated with maternal vascular malperfusion lesions in the placenta of women with preeclampsia. Placenta. 2019;78:29–35. DOI: 10.1016/j.placenta.2019.02.014 |
| [48] |
Schmella M.J., Assibey-Mensah V., Parks W.T., et al. Plasma concentrations of soluble endoglin in the maternal circulation are associated with maternal vascular malperfusion lesions in the placenta of women with preeclampsia // Placenta. 2019. Vol. 78. P. 29–35. DOI: 10.1016/j.placenta.2019.02.014 |
Eсо-Vector
/
| 〈 |
|
〉 |