medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-3-68-73medsovet-5572Research ArticleБеременность и родыPregnancy and childbirthВозможности оптимизации подготовки к беременности при наличии состояний, сопровождающихся эндотелиальной дисфункциейPossibilities of optimization of pregnancy preparation in the presence of conditions accompanied by endothelial dysfunctionhttps://orcid.org/0000-0001-9827-1922ВиноградоваМ. А.VinogradovaM. A.

Виноградова Мария Алексеевна, кандидат медицинских наук, заведующая отделением репродуктивной гематологии и клинической гемостазиологии

117997, Москва, ул. Академика Опарина, д. 4

Mariya A. Vinogradova, Cand. of Sci. (Med.), Head of the Department of Reproductive Hematology and Clinical Hemostasiology

4, Oparina St., Moscow, 117997

mary-grape@ya.ruhttps://orcid.org/0000-0002-6125-590XКирсановаТ. В.KirsanovaT. V.

Кирсанова Татьяна Валерьевна, кандидат медицинских наук, старший научный сотрудник отделения репродуктивной гематологии и клинической гемостазиологии

117997, Москва, ул. Академика Опарина, д. 4

Tat’yana V. Kirsanova, Cand. of Sci. (Med.), Senior Researcher, Department of Reproductive Hematology and Clinical Hemostasiology

4, Oparina St., Moscow, 117997

a_tatya@mail.ruhttps://orcid.org/0000-0001-8464-6789СеребрийскаяД. С.SerebriyskayaD. S.

Серебрийская Диана Сергеевна, врач-трансфузиолог отделения репродуктивной гематологии и клинической гемостазиологии

117997, Москва, ул. Академика Опарина, д. 4

Diana S. Serebriyskaya, Transfusiologist of the Department of Reproductive Hematology and Clinical Hemostasiology

4, Oparina St., Moscow, 117997

diaser@inbox.ruНациональный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. академика В.И. КулаковаРоссияNational Medical Research Center for Obstetrics, Gynecology and Perinatology named after academician V.I. KulakovRussian Federation202016042020036873Copyright © Виноградова М.А., Кирсанова Т.В., Серебрийская Д.С., 20202020Виноградова М.А., Кирсанова Т.В., Серебрийская Д.С.Vinogradova M.A., Kirsanova T.V., Serebriyskaya D.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5572

Реализация репродуктивной функции является одной из главных составляющих качества жизни женщин. Несмотря на значительные успехи в терапии бесплодия и профилактике репродуктивных потерь, данные проблемы все еще остаются актуальными. Также важна своевременная диагностика различных патологических процессов для определения тактики подготовки женщин к беременности и дальнейшего ее ведения с учетом патогенетических особенностей заболеваний. Предпринимаются различные попытки оптимизации как диагностических, так и терапевтических подходов. Особое внимание направлено на выделение групп риска и обеспечение максимально эффективной подготовки к беременности, принимая во внимание возможные факторы риска неблагоприятных исходов. Адекватная диагностика фоновой патологии и применение доказанно эффективных методов прегравидарной подготовки способны обеспечить значительное улучшение исходов беременности. Особенности функционирования сосудистой системы способны сказаться как на жизни женщины в целом, так и на исходах беременности. Дисфункция эндотелия – составная часть патогенеза множества нозологий (сахарный диабет, хроническая венозная болезнь, гипертоническая болезнь, аутоиммунная патология и др.). Восстановление нарушения работы эндотелия сосудов и, как следствие, профилактика вероятных сосудистых осложнений – одна из новых целей в превентивном подходе к беременности. Многообещающим центром данного подхода рассматривается препарат сулодексид. Три основных эффекта данного препарата – антитромботический, противовоспалительный и защитный в отношении эндотелия – обеспечивают значительное расширение возможностей подготовки к беременности при многих нозологиях. В данном обзоре представлены основные его особенности и области применения.

The implementation of the reproductive function is one of the main components of women’s quality of life. Despite significant progress in the treatment of infertility and prevention of reproductive losses, these problems are still relevant. It is also important to timely diagnose various pathological processes in order to determine the tactics of preparing women for pregnancy and its further management, taking into account the pathogenetic characteristics of diseases. Various attempts have been made to optimize both diagnostic and therapeutic approaches. Special attention is paid to identifying risk groups and ensuring the most effective preparation for pregnancy, taking into account possible risk factors for adverse outcomes. Adequate diagnostics of background pathology and the use of proven effective methods of pregravid preparation can significantly improve pregnancy outcomes. Peculiarities of the vascular system functioning may affect both the life of the woman in general and the outcome of pregnancy. Endothelial dysfunction is a component of pathogenesis of many nosologies (diabetes mellitus, chronic venous disease, hypertension, autoimmune pathology, etc.). Restoration of vascular endothelial dysfunction and, as a consequence, prevention of probable vascular complications is one of the new goals in the preventive approach to pregnancy. The promising center of this approach is considered to be the drug sulodexide. The three main effects of this drug – antithrombotic, anti-inflammatory and defensive in relation to endothelium – provide a significant increase in pregnancy preparation possibilities in many nosologies. This review presents its main features and areas of use.

дисфункция эндотелиясулодексидрепродуктивные потерихроническая венозная болезньпрегравидарная подготовкаendothelial dysfunctionsulodexidereproductive losseschronic venous diseasepregravid preparationReferencesЧерняховская Н.Е., Шишло В.К., Поваляев А.В. Коррекция микроциркуляции в клинической практике. М.: Бином; 2013. 208 с.Chernyakhovskaya N.E., Shishlo V.K., Povalyaev A.V. Microcirculation correction in clinical practice. Moscow: Binom; 2013. 208 p. (In Russ.)Cicinelli E., De Ziegler D., Nicoletti R., Colafiglio G., Saliani N., Resta L. et al. Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril. 2008;89(3):677–684. doi: 10.1016/j.fertnstert.2007.03.074.Cicinelli E., De Ziegler D., Nicoletti R., Colafiglio G., Saliani N., Resta L. et al. Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril. 2008;89(3):677–684. doi: 10.1016/j.fertnstert.2007.03.074.Kimura F., Takebayashi A., Ishida M., Nakamura A., Kitazawa J., Morimune A. et al. Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res. 2019;45(5):951–960. doi: 10.1111/jog.13937.Kimura F., Takebayashi A., Ishida M., Nakamura A., Kitazawa J., Morimune A. et al. Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res. 2019;45(5):951–960. doi: 10.1111/jog.13937.Hoppensteadt D.A., Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014;33(3):229–235. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24936531.Hoppensteadt D.A., Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014;33(3):229–235. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24936531.Masola V., Zaza G., Onisto M., Lupo A., Gambaro G. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects. Int Angiol. 2014;33:243–254. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24936533.Masola V., Zaza G., Onisto M., Lupo A., Gambaro G. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects. Int Angiol. 2014;33:243–254. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24936533.Zhang X., Sun D., Song J.W., Zullo J., Lipphardt M., Coneh-Gould L., Goligorsky M.S. Endothelial cell dysfunction and glycocalyx – A viscious circle. Matrix Biol. 2018;71–72:421–431. doi: 10.1016/j.matbio.2018.01.026.Zhang X., Sun D., Song J.W., Zullo J., Lipphardt M., Coneh-Gould L., Goligorsky M.S. Endothelial cell dysfunction and glycocalyx – A viscious circle. Matrix Biol. 2018;71–72:421–431. doi: 10.1016/j.matbio.2018.01.026.Veraldi N., Guerrini M., Urso E., Risi G., Bertini S., Bensi D., Bisio A. Fine structural characterization of sulodexide. J Pharm Biomed Anal. 2018;156:67–79. doi: 10.1016/j.jpba.2018.04.012.Veraldi N., Guerrini M., Urso E., Risi G., Bertini S., Bensi D., Bisio A. Fine structural characterization of sulodexide. J Pharm Biomed Anal. 2018;156:67–79. doi: 10.1016/j.jpba.2018.04.012.Coccheri S., Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Devel Ther. 2013;8:49–65. doi: 10.2147/DDDT.S6762.Coccheri S., Mannello F. Development and use of sulodexide in vascular diseases: implications for treatment. Drug Des Devel Ther. 2013;8:49–65. doi: 10.2147/DDDT.S6762.Harenberg J. Review of pharmacodynamics, pharmacokinetics and therapeutic properties of sulodexide. Med Res. 1998;18(1):1–20. doi: 10.1002/(SICI)1098-1128(199801)18:1<1::AID-MED1>3.0.CO;2-4.Harenberg J. Review of pharmacodynamics, pharmacokinetics and therapeutic properties of sulodexide. Med Res. 1998;18(1):1–20. doi: 10.1002/(SICI)1098-1128(199801)18:1<1::AID-MED1>3.0.CO;2-4.Milani M.R., Busutti L., Breccia A. Pharmacokinetics of sulodexide evaluation from 131-labelled fast-moving heparin after single intravenous and oral administration on man at different doses. Brit J Clin Res. 1992;3:161–178.Milani M.R., Busutti L., Breccia A. Pharmacokinetics of sulodexide evaluation from 131-labelled fast-moving heparin after single intravenous and oral administration on man at different doses. Brit J Clin Res. 1992;3:161–178.Carroll B.J., Piazza G., Goldhaber S.Z. Sulodexide in Venous Disease. J Thromb Haemost. 2019;17(1):31–38. doi: 10.1111/jth.14324.Carroll B.J., Piazza G., Goldhaber S.Z. Sulodexide in Venous Disease. J Thromb Haemost. 2019;17(1):31–38. doi: 10.1111/jth.14324.Cosmi B., Cini M., Legnani C., Pancani C., Calanni F., Coccheri S. Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003;109(5–6):333–339. doi: 10.1016/S00493848(03)00246-9.Cosmi B., Cini M., Legnani C., Pancani C., Calanni F., Coccheri S. Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans. Thromb Res. 2003;109(5–6):333–339. doi: 10.1016/S00493848(03)00246-9.Mauro M., Ferraro G., Palmieri G.C. Profibrinolytic and antithrombotic effects of sulodexide oral administration: a double-blind, cross-over, placebocontrolled study. Curr Ther Res. 1992;51:342–350.Mauro M., Ferraro G., Palmieri G.C. Profibrinolytic and antithrombotic effects of sulodexide oral administration: a double-blind, cross-over, placebocontrolled study. Curr Ther Res. 1992;51:342–350.Cerletti C., Rajtar G., Marchi E., De Gaetano G. Interaction between glycosaminoglycans, platelets, and leukocytes. Semin Thromb Hemost. 1994;20(3):245–253. doi: 10.1055/s-2007-1001909.Cerletti C., Rajtar G., Marchi E., De Gaetano G. Interaction between glycosaminoglycans, platelets, and leukocytes. Semin Thromb Hemost. 1994;20(3):245–253. doi: 10.1055/s-2007-1001909.Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122(6):743–752. doi: 10.1016/j.thromres.2006.10.026.Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res. 2008;122(6):743–752. doi: 10.1016/j.thromres.2006.10.026.Ligi D., Croce L., Mosti G., Raffetto J.D., Mannello F. Chronic venous insufficiency: Transforming growth factor-beta isoforms and soluble endoglin concentration in different states of wound healing. Int J Mol Sci. 2017;18(10):2206. doi: 10.3390/ijms18102206.Ligi D., Croce L., Mosti G., Raffetto J.D., Mannello F. Chronic venous insufficiency: Transforming growth factor-beta isoforms and soluble endoglin concentration in different states of wound healing. Int J Mol Sci. 2017;18(10):2206. doi: 10.3390/ijms18102206.Mannello F., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease. Int Angiol. 2014;33(3):236–242. Availale at: https://www.ncbi.nlm.nih.gov/pubmed/24936532.Mannello F., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease. Int Angiol. 2014;33(3):236–242. Availale at: https://www.ncbi.nlm.nih.gov/pubmed/24936532.Mannello F., Ligi D., Canale M., Raffetto J.D. Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors from human macrophages: role of glycosaminoglycans in inflammatory pathways of chronic venous disease. Curr Vasc Pharmacol. 2014;12(1):173–185. doi: 10.2174/1570161111666131126144025.Mannello F., Ligi D., Canale M., Raffetto J.D. Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors from human macrophages: role of glycosaminoglycans in inflammatory pathways of chronic venous disease. Curr Vasc Pharmacol. 2014;12(1):173–185. doi: 10.2174/1570161111666131126144025.Ciszewicz M., Polubinska A., Antoniewicz A., Suminska-Jasinska K., Breborowicz A. Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity. Transl Res. 2009;153(3):118–123. doi: 10.1016/j.trsl.2008.12.007.Ciszewicz M., Polubinska A., Antoniewicz A., Suminska-Jasinska K., Breborowicz A. Sulodexide suppresses inflammation in human endothelial cells and prevents glucose cytotoxicity. Transl Res. 2009;153(3):118–123. doi: 10.1016/j.trsl.2008.12.007.Blich M., Golan A., Arvatz G., Sebbag A., Shafat I., Sabo E. et al. Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression. Arterioscler Thromb Vasc Biol. 2013;33(2):e56– e65. doi: 10.1161/ATVBAHA.112.254961.Blich M., Golan A., Arvatz G., Sebbag A., Shafat I., Sabo E. et al. Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression. Arterioscler Thromb Vasc Biol. 2013;33(2):e56– e65. doi: 10.1161/ATVBAHA.112.254961.Andreozzi G.M. Role of sulodexide in the treatment of CVD. Int Angiol. 2014;33(3):255–262.Andreozzi G.M. Role of sulodexide in the treatment of CVD. Int Angiol. 2014;33(3):255–262.Mannello F., Medda V., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases. Curr Vasc Pharmacol. 2013;11(3):354–365. doi: 10.2174/1570161111311030010.Mannello F., Medda V., Ligi D., Raffetto J.D. Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases. Curr Vasc Pharmacol. 2013;11(3):354–365. doi: 10.2174/1570161111311030010.Ligi D., Mosti G., Croce L., Raffetto J.D., Mannello F. Chronic venous disease – part II: Proteolytic biomarkers in wound healing. Biochim Biophys Acta (BBA). 2016;1862(10):1900–1908. doi: 10.1016/j.bbadis.2016.07.011.Ligi D., Mosti G., Croce L., Raffetto J.D., Mannello F. Chronic venous disease – part II: Proteolytic biomarkers in wound healing. Biochim Biophys Acta (BBA). 2016;1862(10):1900–1908. doi: 10.1016/j.bbadis.2016.07.011.Meissner M.H., Eklof B., Smith P.C., Dalsing M.C., DePalma R.G., Gloviczki P. et al. Secondary chronic venous disorders. J Vasc Surg. 2007;46(6):S68S– S83. doi: 10.1016/j.jvs.2007.08.048.Meissner M.H., Eklof B., Smith P.C., Dalsing M.C., DePalma R.G., Gloviczki P. et al. Secondary chronic venous disorders. J Vasc Surg. 2007;46(6):S68S– S83. doi: 10.1016/j.jvs.2007.08.048.Chatterjee S. Endothelial mechanotransduction, redox signaling and the regulation of vascular inflammatory pathways. Front Physiol. 2018;9:1–16. doi: 10.3389/fphys.2018.00524.Chatterjee S. Endothelial mechanotransduction, redox signaling and the regulation of vascular inflammatory pathways. Front Physiol. 2018;9:1–16. doi: 10.3389/fphys.2018.00524.Bergan J.J., Schmid-Schönbein G.W., Coleridge Smith P.D., Nicolaides A.N., Boisseau M.R., Eklof B. Chronic venous disease. N Engl J Med. 2006;355:488–498. doi: 10.1056/NEJMra055289.Bergan J.J., Schmid-Schönbein G.W., Coleridge Smith P.D., Nicolaides A.N., Boisseau M.R., Eklof B. Chronic venous disease. N Engl J Med. 2006;355:488–498. doi: 10.1056/NEJMra055289.Elleuch N., Zidi H., Bellamine Z., Hamdane A., Guerchi M., Jellazi N. Sulodexide in patients with chronic venous disease of the lower limbs: clinical efficacy and impact on quality of life. Adv Ther. 2016;33:1536– 1549. doi: 10.1007/s12325-016-0359-9.Elleuch N., Zidi H., Bellamine Z., Hamdane A., Guerchi M., Jellazi N. Sulodexide in patients with chronic venous disease of the lower limbs: clinical efficacy and impact on quality of life. Adv Ther. 2016;33:1536– 1549. doi: 10.1007/s12325-016-0359-9.Raffetto J.D. Dermal pathology, cellular biology, and inflammation in chronic venous disease. Thromb Res. 2009;123:S66–S71. doi: 10.1016/S0049-3848(09)70147-1.Raffetto J.D. Dermal pathology, cellular biology, and inflammation in chronic venous disease. Thromb Res. 2009;123:S66–S71. doi: 10.1016/S0049-3848(09)70147-1.Mansilha A., Sousa J. Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int J Mol Sci. 2018;19(6):1–21. doi: 10.3390/ijms19061669.Mansilha A., Sousa J. Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int J Mol Sci. 2018;19(6):1–21. doi: 10.3390/ijms19061669.Kearon C., Kahn S.R., Agnelli G., Goldhaber S., Raskob G.E., Comerota A.J. Antithrombotic therapy for venous thromboembolic disease: American College of Chest physicians evidence-based clinical practice guidelines (8th ed.). Chest. 2008;133(6):454S–545S. doi: 10.1378/chest.08-0658.Kearon C., Kahn S.R., Agnelli G., Goldhaber S., Raskob G.E., Comerota A.J. Antithrombotic therapy for venous thromboembolic disease: American College of Chest physicians evidence-based clinical practice guidelines (8th ed.). Chest. 2008;133(6):454S–545S. doi: 10.1378/chest.08-0658.Engberink O., Rorije N.M., Lambers Heersprink H.J., Zeeuw D.D., Born van den B.-J.H., Vogt L. The blood pressure lowering potential of sulodexide – a systematic review and meta-analysis. Br J Clin Pharmacol. 2015;80(6):1245–1253. doi: 10.1111/bcp.12722.Engberink O., Rorije N.M., Lambers Heersprink H.J., Zeeuw D.D., Born van den B.-J.H., Vogt L. The blood pressure lowering potential of sulodexide – a systematic review and meta-analysis. Br J Clin Pharmacol. 2015;80(6):1245–1253. doi: 10.1111/bcp.12722.Кузнецова И.В. Роль преконцепционной эндотелиальной дисфункции в развитии акушерских осложнений. Медицинский алфавит. 2019;1(1):53–58. doi: 10.33667/2078-5631-2019-1-1(376)-53-58.Kuznetsova I.V. Role of preconception endothelial dysfunction in development of obstetric complications. Meditsinskiy alfavit = Medical alphabet. 2019;1(1):53–58. (In Russ.) doi: 10.33667/2078-5631-2019-11(376)-53-58.

The authors declare that there are no conflicts of interest present.