Prognostic value of anti- and proangiogenic factors in severe preeclampsia

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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.

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作者简介

Margarita Vasileva

Almazov National Medical Research Center

编辑信件的主要联系方式.
Email: margo-m1@yandex.ru
ORCID iD: 0000-0001-5253-3958
SPIN 代码: 8495-1800
Scopus 作者 ID: 57204057577

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Ilya Smirnov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Academician A.M. Granov Russian Research Center for Radiology and Surgical Technologies

Email: smirnov.iv.mail@gmail.com
ORCID iD: 0000-0002-1341-825X
SPIN 代码: 7692-0982

Cand. Sci. (Biol.)

俄罗斯联邦, Saint Petersburg; Saint Petersburg

Valentina Ishkaraeva

Almazov National Medical Research Center

Email: ishkaraeva_vv@almazovcentre.ru
ORCID iD: 0000-0002-5391-7600
SPIN 代码: 7668-0607

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Natalya Yakovleva

Almazov National Medical Research Center

Email: natalis.1986@mail.ru
SPIN 代码: 3806-9335

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Elena Vasilyeva

Almazov National Medical Research Center

Email: elena-almazlab@yandex.ru
ORCID iD: 0000-0002-2115-8873
SPIN 代码: 8546-5546
Scopus 作者 ID: 57188759977

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Sergey Chepanov

Almazov National Medical Research Center

Email: chepanovsv@gmail.com
ORCID iD: 0000-0001-6087-7152
SPIN 代码: 6642-6837
Scopus 作者 ID: 56399329700

MD, Cand. Sci. (Med.)

俄罗斯联邦, Saint Petersburg

Lyudmila Kalosha

Almazov National Medical Research Center

Email: ludak070809@gmail.com
俄罗斯联邦, Saint Petersburg

Olga Tamakhina

Almazov National Medical Research Center

Email: tamahinaolgaa@mail.ru
俄罗斯联邦, Saint Petersburg

Sergey Selkov

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: selkovsa@mail.ru
ORCID iD: 0000-0003-1560-7529
SPIN 代码: 7665-0594
Scopus 作者 ID: 6507854443

MD, Dr. Sci. (Med.), Professor, Honored Worker of Science of the Russian Federation

俄罗斯联邦, Saint Petersburg

Irina Zazerskaya

Almazov National Medical Research Center

Email: zazera@mail.ru
ORCID iD: 0000-0003-4431-3917
SPIN 代码: 5683-6741
Scopus 作者 ID: 55981393900

MD, Dr. Sci. (Med.), Professor

俄罗斯联邦, Saint Petersburg

参考

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2. Fig. 1. Indications for emergency cesarean section. TMA — thrombotic microangiopathy; HELLP — free hemoglobin in serum and urine, increased alanine aminotransferase and aspartate aminotransferase activities and thrombocytopenia

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3. Fig. 2. ROC curve characterizing the probability dependence of severe preeclampsia developing on serum soluble endoglin level. Area under the ROC curve is 0.852 ± 0.052 with 95 % confidence interval 0.750–0.954. The model was statistically significant (p < 0.001)

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4. Fig. 3. Analysis of the sensitivity and specificity of the model depending on the threshold values of serum soluble endoglin level

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5. Fig. 4. ROC curve characterizing the probability dependence of severe preeclampsia developing on urine soluble endoglin level. Area under the ROC curve is 0.740 ± 0.079 with 95 % confidence interval 0.585–0.896. The resulting model was statistically significant (p < 0.007)

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6. Fig. 5. Analysis of the sensitivity and specificity of the model depending on the threshold values of urine soluble endoglin level

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7. Fig. 6. Median urine soluble endoglin level conditioning on proteinuria 24-hour urine collection

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8. Fig. 7. Median urine soluble endoglin level conditioning on proteinuria in single portions of urine

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9. Fig. 8. Median serum soluble endoglin level conditioning on fetal-placental blood flow violation

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10. Fig. 9. Median soluble tyrosine kinase-1 and placental growth factor ratio conditioning on fetal-placental blood flow violation

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11. Fig. 10. Regression line characterizing the dependence of delivery term on serum placental growth factor level

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12. Fig. 11. Regression line characterizing the dependence of duration of treatment before delivery on urine soluble endoglin level

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