Клинико-генетические аспекты менопаузальной гормональной терапии - современная парадигма. Что изменила пандемия COVID-19?

In the modern paradigm of public health protection, much attention is paid to the health of women in peri- and postmenopause, and a personalized approach prevails. It is generally recognized that the pathogenetic therapy of menopausal disorders is hormone therapy. But the COVID-19 pandemic has made its own adjustments to the routine strategy of choosing menopausal hormone therapy (MHT). The purpose of this review was to analyze studies on the dependence of the effectiveness of MHT on clinical and genetic aspects in the context of the ongoing COVID-19 pandemic. The review highlights the main risks of MHT for thromboembolic diseases and coagulation complications characteristic of COVID-19, discusses genetic predispositions that aggravate the course of the post-COVID period, as well as the effectiveness of estrogens in protecting the vascular endothelium and increasing the number of CD4+ T cells, providing an adequate immune response when infected with SARS-CoV-2. Numerous studies show that the complications characteristic of the severe course of COVID-19 are multifactorial in nature and cannot be unambiguously explained only by genetic predisposition. However, with the development of personalized medicine, special attention should be paid to the study of genetic aspects that can equally contribute to the occurrence of menopausal disorders in healthy women and aggravate the course of the post-pregnancy period. The data presented allow us to conclude that in the context of the ongoing COVID-19 pandemic at the population level, MHT can bring significant benefits to women during menopause due to the beneficial effect of estrogens on vascular walls. Additional study of the relationship between the course of the postcovid period in MHT users and polymorphisms of candidate genes that determine the risks of thrombotic complications and metabolic consequences is required.В современной парадигме охраны здоровья населения здоровью женщин в пери- и постменопаузе уделяется большое внимание, причем господствует персонифицированный подход. Общепризнанно, что патогенетической терапией менопаузальных расстройств является гормональная терапия. Но пандемия COVID-19 внесла свои коррективы в рутинную стратегию выбора менопаузальной гормональной терапии (МГТ). Целью данного обзора являлся анализ исследований зависимости эффективности МГТ от клинико-генетических аспектов в условиях продолжающейся пандемии COVID-19. В обзоре выделяются основные риски МГТ тромбоэмболических заболеваний и коагуляционных осложнений, характерных для COVID-19, обсуждаются генетические предрасположенности, отягчающие течение постковидного периода, а также эффективность эстрогеныов, защищающих эндотелий сосудов и увеличивающих количество CD4+ T-клеток, обеспечивая адекватный иммунный ответ при инфицировании SARS-CoV-2. Многочисленные исследования показывают, что осложнения, характерные для тяжелого течения COVID-19, носят многофакторный характер и не могут быть однозначно объяснены только генетической предрасположенностью. Однако, с развитием персонализированной медицины, особого внимания заслуживает исследование генетических аспектов, которые могут в равной мере способствовать возникновению менопаузальных расстройств у здоровых женщин и отягощать течение постковидного периода. Приведенные данные позволяют сделать вывод, что в условиях продолжающейся пандемии COVID-19 на популяционном уровне МГТ может принести существенную выгоду женщинам в период климактерия за счет благоприятного влияния эстрогенов на стенки сосудов. Требуется дополнительное изучение взаимосвязи течения постковидного периода у пользовательниц МГТ и полиморфизмов генов-кандидатов, определяющих риски тромботических осложнений и метаболических последствий

Association of the DNA Methyltransferase and Folate Cycle Enzymes’ Gene Polymorphisms with Coronary Restenosis

Background: In recent years, the interest in genetic predisposition studies for coronary artery disease and restenosis has increased. Studies show that polymorphisms of genes encoding folate cycle and homocysteine metabolism enzymes significantly contribute to atherogenesis and endothelial dysfunction. The purpose of this study was to examine some SNPs of genes coding for folate cycle enzymes and DNA methyltransferases as risk factors for in-stent restenosis. Methods: The study included 113 patients after stent implantation and 62 patients without signs of coronary artery disease at coronary angiography as the control group. Real-time PCR and RFLP-PCR were applied to genotype all participants for MTHFR rs1801133, MTHFR rs1801131, MTR rs1805087, MTRR rs1801394, DNMT1 rs8101626, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms. Statistical data processing was carried out using the R language and the SPSS Statistics 20 software. Results: Statistically significant differences in the DNMT3B gene polymorphisms were found between patients with and without in-stent restenosis. An association of TT rs1569686 and TT rs2424913 genotypes with the development of restenosis was revealed. The TT rs1569686 genotype was more frequent in the patients under the age of 65 years and in the subgroup of patients with post-12-month restenosis, as was the minor GG genotype for MTR rs1805087. The homozygous TT genotype for MTHFR rs1801133 was significantly more frequent in the subgroup over 65 years old. The frequencies of the heterozygous genotype for the MTRR gene and the minor GG homozygotes for the DNMT1 gene were significantly higher in the subgroup with in-stent restenosis under 65 years old. Conclusions: The results of this study could be used for a comprehensive risk assessment of ISR development, determining the optimal tactics and an individual approach in the treatment of patients with coronary artery disease before or after percutaneous coronary interventions, including homocysteine-lowering treatment in patients with hyperhomocysteinemia and a high risk of in-stent restenosis

Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

Artificial light is characterized by certain features of its impact on the body in terms of its spectral distribution of power, duration of exposure and intensity. Short waves, perceived as blue light, are the strongest synchronizing agent for the circadian system. In the present work, we investigated the features of the circadian rhythms of blood pressure (BP), heart rate (HR), the excretion of electrolytes and the secretion of melatonin in normotensive (Wistar–Kyoto) and hypertensive (SHR) rats under the action of monochromatic blue light in the daytime period. It was found that the exposure of Wistar–Kyoto rats to monochromatic blue light was accompanied by a significant decrease in nighttime and 24 h systolic BP. The most remarkable changes are characteristic of the HR in SHR rats under monochromatic light. A significant decrease in HR in each time period was found, but the predominance of nighttime over daytime values remained in SHR animals. There was also a significant increase in the mesor of the HR in SHR rats. Additionally, the amplitude of diastolic BP and HR, as well as the range of oscillations in HR, were significantly increased compared with the standard light pattern. In contrast to SHR rats, the regulation of the circadian rhythms in Wistar–Kyoto rats was more flexible and presented more changes, which may be aimed at the adaptation of the body to environmental conditions. For Wistar–Kyoto rats, an increase in the level of excreted electrolytes was observed under the action of monochromatic light, but no similar changes were found in SHR rats. For Wistar–Kyoto rats, a significant decrease in the urine concentration of aMT6s in the daytime and nighttime periods is characteristic, which results in the loss of the circadian rhythm. In SHR rats, there was a significant decrease in the nighttime content of aMT6s in the urine, while the daytime concentration, on the contrary, increased. The obtained data demonstrate that prolonged exposure to monochromatic blue light in the daytime period affects the circadian structure of the rhythms of the cardiovascular system, the rhythm of electrolyte excretion and the production of epiphyseal melatonin in wild-type and hypertensive animals. In SHR rats, the rhythms of BP and HR exhibit a more rigid pattern