GynecologyGynecologyГинекология2079-56962079-5831Consilium Medicum28247ArticlesСтатьиResearch ArticleFolate deficiency elimination: basic strategy homocysteine dependent correction of endothelial dysfunctionУстранение дефицита фолатов – основная стратегия коррекции гомоцистеинзависимой эндотелиальной дисфункцииTapilskayaN IТапильскаяНаталья Игоревна

д-р мед. наук, проф. каф. акушерства и гинекологии, проф. каф. онкологии

tapnatalia@yandex.ruGaidukovS NГайдуковСергей Николаевич

д-р мед. наук, проф., зав. каф. акушерства и гинекологии

ГБОУ ВПО Санкт-Петербургский государственный педиатрический медицинский университет Минздрава РФ15062013153VOL 15, NO3 (2013)ТОМ 15, №3 (2013)707409042020Copyright ©; 2013, Consilium MedicumCopyright ©; 2013, ООО "Консилиум Медикум"2013Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://gynecology.orscience.ru/2079-5831/article/view/28247

Endothelial dysfunction is one of the most important pathogenetic mechanisms of both cardiovascular disease and uterine-placental microcirculation. Recent research shows that homocysteine plays a role of a forthcoming universal pathogenic factor in the case of mechanisms regulating cellular homeostasis depletion, namely, in a long flowing hyperhomocysteinemia by an imbalance in the antioxidant system of the body leads to a decrease in the number of endothelial progenitor cells, which reduces the regenerative capacity and plasticity of the vascular wall. Hyperhomocysteine when administered in excessive concentrations leads to inhibition of sodium-potassium adenosinetriphosphatase in the membrane of vascular smooth muscle cells, increasing intracellular sodium concentration, and thus leading to electrolyte disturbances that cause vasoconstriction becoming and essential element is a vicious circle of the underlying pathogenesis of both hypertension and preeclampsia. The use of contraceptives containing biologically active folate metafolin on preconception stage is a part of a targeted approach to the prevention of complications of pregnancy in women of reproductive age.

Дисфункция эндотелия является одним из важнейших патогенетических механизмов как сердечно-сосудистых заболеваний, так и маточно-плацентарной микроциркуляции. Исследованиями последних лет показано, что гомоцистеин играет роль универсального патогенетического фактора, выходящего на первый план в случае истощения механизмов регулирования клеточного гомеостаза, а именно длительно протекающая гипергомоцистеинемия посредством дисбаланса в антиоксидантной системе организма приводит к снижению количества эндотелиальных прогениторных клеток, что снижает регенеративные возможности и пластичность сосудистой стенки. Гипергомоцистеин в избыточных концентрациях приводит к угнетению натрий-калиевой аденозинтрифосфатазы в мембране гладкомышечных клеток сосудов, увеличивает внутриклеточную концентрацию натрия, приводит к электролитным нарушениям, что вызывает вазоконстрикцию и становится существенным элементом порочного круга, лежащего в основе патогенеза как артериальной гипертензии, так и преэклампсии. Применение контрацептивов, содержащих в своем составе биологически активный фолат метафолин, на этапе преконцепции является частью целевого подхода к профилактике осложнений беременности у женщин репродуктивного возраста.

homocysteineendothelial dysfunctionmetafolincombined oral contraceptives, folate containingгомоцистеинэндотелиальная дисфункцияметафолинкомбинированные оральные контрацептивы, содержащие фолатыПетрищев H.H., Власов Т.Д. Тромбогенные и тромборезистентные свойства эндотелия. Система гемостаза. Под ред. H.H.Петрищева. Спб.: Издательство СпбГМУ, 2003; с. 27–40.Гайдуков С.Н., Аверина И.В. Современные подходы к диагностике и прогнозированию гестоза у беременных. Казан. мед. журн.: Издание Министерства здравоохранения Татарстана и Казанского государственного медицинского университета. 2011; 92 (1): 127–31.Jakubowski H, Głowacki R. Chemical biology of homocysteine thiolactone and related metabolites. Adv Clin Chem 2011; 55: 81–103.Undas A, Stepień E, Glowacki R et al. Folic acid administration and antibodies against homocysteinylated proteins in subjects with hyperhomocysteinemia. Thromb Haemost 2006; 96 (3): 342–7.Stroylova Y.Y, Chobert J.M, Muronetz V.I et al. N - homocysteinylation of ovine prion protein induces amyloid - like transformation. Arch Biochem Biophys 2012; 526 (1): 29–37.Borowczyk K, Shih D.M, Jakubowski H. Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a protective role of paraoxonase 1. J Alzheimers Dis 2012; 30 (2): 225–31.Rasic-Markovic A, Stanojlovic O, Hrncic D et al. The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 2009; 327: 39–45.Bogdanski P, Miller-Kasprzak E, Pupek-Musialik D et al. Plasma total homocysteine is a determinant of carotid intima - media thickness and circulating endothelial progenitor cells in patients with newly diagnosed hypertension. Clin Chem Lab Med 2012; 50 (6): 1107–13.Fujiki Y, Hirashima Y, Seshimo S et al. Homocysteine induced SH-SY5Y apoptosis through activation of NADPH oxidase in U251MG cells. Neurosci Res 2012; 72 (1): 9–15.Sunden S.L, Renduchintala M.S, Park E.I et al. Betaine - homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 1997;345 (1): 171–4.Robertson K.D. DNA methylation, methyltransferases, and cancer. Oncogene 2001; 20 (24): 3139–55.Jacques P.F, Bostom A.G, Wilson P.W et al. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73 (3): 613–21.van der Molen E.F, Arends G.E, Nelen W.L et al. A common mutation in the 5-, 10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy. Am J Obstet Gynecol 2000; 182 (5): 1258–63.Peerbooms O.L, van Os J, Drukker M et al. Meta - analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun 2011; 25 (8): 1530–43.Allen N.C, Bagade S, Mc Queen M.B et al. Systematic meta - analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nature 2008; 40: 827–34.Maarten van den Buuse. Modelling the positive symptoms of schizophrenia in genetically modified mice: pharmacology and methodology aspects. Schizophr Bull 2010; 36 (2): 246–70.Muntjewerff J.W, Kahn R.S, Blom H.J, den Heijer M. Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta - analysis. Mol Psychiatr 2006; 11 (2): 143–9.Mabrouk H, Douki W, Mechri A et al. Hyperhomocysteinemia and schizophrenia: case control study. Hyperhomocysteinemia and schizophrenia: case control study. Encephale 2011; 37 (4): 308–13.Brenner B, Kupferminc M.J. Inherited thrombophilia and poor pregnancy outcome. Best Pract Res Clin Obstet Gynaecol 2003; 17 (3): 427–39.Vollset S.E, Refsum H, Irgens L.M et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine study. Am J Clin Nutr 2000; 71 (4): 962–8.Streck E.L, Bavaresco C.S, Netto C.A, Wyse A.T. Chronic hyperhomocysteinemia provokes a memory deficit in rats in the Morris water maze task. Behav Brain Res 2004; 153 (2): 377–81.Baydas G, Koz S.T, Tuzcu M et al. Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring. Int J Dev Neurosci 2007; 25 (3): 133–9.Qureshi I, Chen H, Brown A.T et al. Homocysteine - induced vascular dysregulation is mediated by the NMDA receptor. Vasc Med 2005; 10 (3): 215–23.Schaub C, Uebachs M, Beck H, Linnebank M. Chronic homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons. Exp Brain Res 2013; 225 (4): 527–34.Poddar R, Paul S. Homocysteine - NMDA receptor - mediated activation of extracellular signal - regulated kinase leads to neuronal cell death. J Neurochem 2009; 110 (3): 1095–106.MCGowan M.H, Russell P, Carper D.A. Na+, K+-ATPase inhibitors down - reglate gene expression of the intracelluiar signaling protein 14-3-3 in rat lens. J Pharmacol. Exp Ther 1999; 289: 1559–63.Schoner W. Endogenous cardiac glicosides, a new class of steroid hormones. Eur J Biocem 2002; 269: 2440–8.Fedorova O.V, Tapilskaya N.I, Bzhelyansky A.M et al. Interaction of Digibind with endogenous cardiotonic steroids from preeclamptic placentae. J Hypertens 2010; 28 (2): 361–6.Cartier L, Hartley O, Dubois-Dauphin M, Krause K.H. Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 2005; 48 (1): 16–42.Van Eldik L.J, Wainwright M.S. The Janus face of glial - derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci 2003; 21 (3–4): 97–108.Huttunen H.J, Kuja-Panula J, Sorci G et al. Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation. J Biol Chem 2000; 275 (51): 40096–105.Reali C, Scintu F, Pillai R et al. S100b counteracts effects of the neurotoxicant trimethyltin on astrocytes and microglia. J Neurosci Res 2005; 81 (5): 677–86.Wainwright M.S, Craft J.M, Griffin W.S et al. Increased susceptibility of S100B transgenic mice to perinatal hypoxia - ischemia. Ann Neurol 2004; 56 (1): 61–7.Sorci G, Agneletti A.L, Donato R. Effects of S100A1 and S100B on microtubule stability. An in vitro study using triton - cytoskeletons from astrocyte and myoblast cell lines. Neuroscience 2000; 99 (4): 773–83.Xiong Z, O’Hanlon D, Becker L.E et al. Enhanced calcium transients in glial cells in neonatal cerebellar cultures derived from S100B null mice. Exp Cell Res 2000; 257 (2): 281–9.Bianchi R, Kastrisianaki E, Giambanco I, Donato R. S100B protein stimulates microglia migration via RAGE - dependent up - regulation of chemokine expression and release. J Biol Chem 2011; 286 (9): 7214–26.Undas A, Jarkowski M, Twardowska M et al. Antibodies to N - homocysteinylated albumin as a marker for early - onset coronary artery disease in men. Thromb Haemost 2005; 93: 346–50.Zhou J, Austin R.C. Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms 11. Biofactors 2009; 35 (2): 120–9.Lentz S.R. Mechanisms of homocysteine - induced atherothrombosis. J Thromb Haemost 2005; 3: 1646–54.Mc Cully K.S. Vascular pathology of homocysteinemia: implications for the pathogenesis of atherosclerosis. Am J Pathol 1969; 56: 111–28.