Clinical significance of expression of the marker of adaptation to hypoxia HIF-1α in pregnant women with initial forms of venous disease
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.208
Abstract
Aim: to study the activity of the HIF-1á (hypoxia-inducible factor-1á) hypoxia marker in pregnant women with phlebopathy and its relationship with placenta morphological changes and perinatal complications.
Materials and Methods. 70 women with phlebopathy were dynamically examined during pregnancy. The main group consisted of 30 patients with newborns showing signs of hypoxia; the control group consisted of 40 women with healthy children. All women underwent ultrasound examinations of the lower extremity veins and pelvis by assessing vascular patency, state of venous valves, and intensity of platelet sludge. Expression of the HIF-1á transcription factor at gestational age of 18–20 and 36 weeks was performed by using real-time polymerase chain reaction.
Results. Altered functional state of the veins was found in all pregnant women from the main group, which was accompanied by formation of varying degree platelet sludge in the area of the venous valves in the majority of women, as well as signs of endothelial dysfunction and venous hypoxia highlighted with HIF1-á gene expression upregulated by 2.18-fold. No changes in such parameters were observed in control group.
Conclusion. The transcription factor HIF1-á can be considered as a marker of unfavorable perinatal outcomes in pregnant women with signs of phlebopathy.
About the Authors
E. Iu. IupatovRussian Federation
Evgenii Iu. Iupatov – MD, PhD, Associate Professor, Head of the Department of Obstetrics and Gynecology, Kazan State Medical Academy; Associate Professor, Department of Surgery and Postgraduate Education, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University; Scopus Author ID: 57201192778
11 Mushtari Str., Kazan 420012
18 Kremlevskaya Str., Kazan 420008
L. I. Maltseva
Russian Federation
Larisa I. Maltseva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology
11 Mushtari Str., Kazan 420012
T. P. Zefirova
Russian Federation
Tatiana P. Zefirova – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology
11 Mushtari Str., Kazan 420012
R. S. Zamaleeva
Russian Federation
Roza S. Zamaleeva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology
11 Mushtari Str., Kazan 420012
I. M. Ignatiev
Russian Federation
Igor М. Ignatiev – MD, Dr Sci Med, Corresponding Member of the Academy of Sciences of the Republic of Tatarstan, Professor, Department of Cardiovascular and Endovascular Surgery
49 Butlerova Str., Kazan 420012
O. A. Kravtsova
Russian Federation
Olga A. Kravtsova – MD, PhD, Associate Professor, Department of Biochemistry and Biotechnology, Institute of Fundamental Medicine and Biology
18 Kremlevskaya Str., Kazan 420008
References
1. Milman N., Graudal N., Nielsen O.J., Agger A.O. Serum erythropoietin during normal pregnancy: relationship to hemoglobin and iron status markers and impact of iron supplementation in a longitudinal, placebo-controlled study on 118 women. Int J Hematol. 1997;66(2):159–68. https://doi.org/10.1016/s0925-5710(97)00031-5. PMID: 9277046.
2. Bille-Brahe N.E., Rørth M. Red cell 2.3-diphosphoglycerate in pregnancy. Acta Obstet Gynecol Scand. 1979;58(1):19–21. https://doi.org/10.3109/00016347909154906. PMID: 419949.
3. de Haas S., Ghossein-Doha C., van Kuijk S.M. et al. Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017;49(2):177–87. https://doi.org/10.1002/uog.17360. PMID: 28169502.
4. Nadel A.S., Ballermann B.J., Anderson S., Brenner B.M. Interrelationships among atrial peptides, renin, and blood volume in pregnant rats. Am J Physiol. 1988;254(5 Pt 2):R793–800. https://doi.org/10.1152/ajpregu.1988.254.5.R793.
5. Bitsadze V.O., Makatsariya A.D., Khizroeva J.Kh. et al. Thrombophilia as the most important link in the pathogenesis of pregnancy complications. [Trombofiliya kak vazhnejshee zveno patogeneza oslozhnenij beremennosti]. Prakticheskaya medicina. 2012;(5):22–9. (In Russ.).
6. Stoyko Yu.M., Kirienko A.I., Zatevakhin I.I. et al. Russian clinical guidelines for the diagnosis and treatment of chronic venous diseases. [Rossijskie klinicheskie rekomendacii po diagnostike i lecheniyu i hronicheskih zabolevanij ven]. Phlebology. 2018;12(3):146–240. (In Russ.).
7. Gardenghi L.A., Dezotti N.R.A., Dalio M.B. et al. Lower limb venous diameters and haemodynamics during pregnancy and postpartum period in healthy primigravidae. Phlebology. 2017;32(10):670–8. https://doi.org/10.1177/0268355516671586.
8. Serov V.N., Zharov E.V. Current principles of diagnosis and treatment of chronic venous insufficiency in pregnant women. [Sovremennye principy diagnostiki i lecheniya hronicheskoj venoznoj nedostatochnosti u beremennyh]. Moscow: FGU Nauchnyj centr akusherstva, ginekologii i perinatologii Rosmedtekhnologij, 2007. 24 p. (In Russ.).
9. Serebrovskaya T.V. Hypoxia-inducible factor: role in the pathophysiology of respiration (review). [Gipoksiya-inducibel'nyj faktor: rol' v patofiziologii dyhaniya (obzor)]. Ukrainskij pul'monologicheskij zhurnal. 2005;(3):77–81. (In Russ.).
10. Ignatiev I.M., Bredikhin R.A., Akhunova S.Yu. Importance of venous tone in the diagnosis of varicose veins. [Znachenie venoznogo tonusa v diagnostike varikoznoj bolezni]. Ul'trazvukovaya i funkcional'naya diagnostika. 2002;(4):76–81. (In Russ.).
11. Ignatiev I.M., Bredikhin R.A., Fomina E.E. Ultrasonographic diagnosis of venous thromboses. [Ul'trazvukovaya diagnostika venoznyh trombozov]. Angiologiya i sosudistaya hirurgiya. 2009;15(4):35–9. (In Russ.).
12. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8. https://doi.org/10.1006/meth.2001.1262. PMID: 11846609.
13. Caniggia I., Winter J.L. Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in normal and pre-eclamptic pregnancies – a review. Рlacenta. 2002;23(Suppl A):S47–57. https://doi.org/10.1053/plac.2002.0815.
14. Lee Y.M., Ting A.C., Cheng S.W. Diagnosing deep vein thrombosis in the lower extremity: correlation of clinical and duplex scan findings. Hong Kong Med J. 2002;8(1):9–11.
15. Tsukanov Yu.T. Medicinal treatment of vascular diseases. [Lekarstvennoe lechenie zabolevanij sosudov]. Omsk: Omich, 1992. 102 p. (In Russ.).
16. Cropmaer K.P. Placental disorders in pregnant women with varicose veins. [Placentarnye narusheniya u beremennyh s varikoznoj bolezn'yu]. Avtoref. dis. kand. med. nauk. Omsk, 2012. 22 p. (In Russ.).
17. Kurlak L.O., Williams P.J., Bulmer J.N. et al. Placental expression of adenosine A(2A) receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system. Placenta. 2015;36(5):611–3. https://doi.org/10.1016/j.placenta.2015.02.011. PMID: 25745823.
18. Tissot van Patot M.C., Bendrick-Peart J., Beckey V.E. et al. Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia. Am J Physiol Lung Cell Mol Physiol. 2004;287(3):L525–32. https://doi.org/10.1152/ajplung.00203.2003. PMID: 15132953.
19. García-Honduvilla N., Ortega M.A., Asúnsolo A. et al. Placentas from women with pregnancy-associated venous insufficiency show villi damage with evidence of hypoxic cellular stress. Hum Pathol. 2018;77:45–53. https://doi.org/10.1016/j.humpath.2018.03.022. PMID: 29626597.
Review
For citations:
Iupatov E.I., Maltseva L.I., Zefirova T.P., Zamaleeva R.S., Ignatiev I.M., Kravtsova O.A. Clinical significance of expression of the marker of adaptation to hypoxia HIF-1α in pregnant women with initial forms of venous disease. Obstetrics, Gynecology and Reproduction. 2021;15(3):276-286. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.208

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