Appointment of lipid-lowering therapy in the Russian population: comparison of SCORE and SCORE2 (according to the ESSE-RF study)

Aim. In 2021, the European Society of Cardiology (ESC) guidelines for the prevention of cardiovascular diseases (CVDs) were published, where a new SCORE2 CVD risk assessment model was introduced. In our work, we compared approaches to determine the indications for initiating lipid-lowering therapy in the Russian population aged 25-64 years according to the guidelines for the diagnosis and treatment of lipid metabolism disorders of the Russian National Atherosclerosis Society (2020) and ESC guidelines for CVD prevention (2021).Material and methods. The ESSE-RF epidemiological study was conducted in 12 Russian regions. All participants signed informed consent and completed approved questionnaires. We performed anthropometric and blood pressure (BP) measurements, as well as fasting blood sampling. In total, 20665 people aged 25-64 years were examined. The analysis included data from 19546 respondents (women, 12325 (63,1%)).Results. Of the 19546 participants, 3828 (19,6%) were classified as high or very high CV risk based on the 9 criteria: BP ≥180/110 mm Hg, total cholesterol >8,0 mmol/l, low-density lipoprotein (LDL) >4,9 mmol/l, lipid-lowering therapy, chronic kidney disease (CKD) with glomerular filtration rate <60 ml/min/1,73 m2, type 2 diabetes, previous stroke and/or myocardial infarction. Of 3828 people, lipidlowering therapy was indicated in 3758 (98%) (criteria for LDL ≥1,8 mmol/l and LDL ≥1,4 mmol/l, respectively, high and very high risk). In addition, 5519 individuals aged <40 years were excluded from further analysis due to the lower age threshold of models. For 10199 participants aged >40 years without established CVD, diabetes, CKD, cardiovascular risk stratification was performed according to the SCORE and SCORE2. Of them, according to the Russian National Atherosclerosis Society (2020) and ESC 2021 guidelines, lipid-lowering therapy was indicated for 701 and 9487 participants, respectively.Conclusion. Using the new approach proposed by the ESC in 2021, the number of patients aged 40-64 years without CVD, diabetes and CKD with indications for lipidlowering therapy for primary prevention in Russia increases by 14 times compared with the 2020 Russian National Atherosclerosis Society guidelines

Protecting a transgene expression from the HAC-based vector by different chromatin insulators

Human artificial chromosomes (HACs) are vectors that offer advantages of capacity and stability for gene delivery and expression. Several studies have even demonstrated their use for gene complementation in gene-deficient recipient cell lines and animal transgenesis. Recently, we constructed an advance HAC-based vector, alphoid(tetO)-HAC, with a conditional centromere. In this HAC, a gene-loading site was inserted into a centrochromatin domain critical for kinetochore assembly and maintenance. While by definition this domain is permissive for transcription, there have been no long-term studies on transgene expression within centrochromatin. In this study, we compared the effects of three chromatin insulators, cHS4, gamma-satellite DNA, and tDNA, on the expression of an EGFP transgene inserted into the alphoid(tetO)-HAC vector. Insulator function was essential for stable expression of the transgene in centrochromatin. In two analyzed host cell lines, a tDNA insulator composed of two functional copies of tRNA genes showed the highest barrier activity. We infer that proximity to centrochromatin does not protect genes lacking chromatin insulators from epigenetic silencing. Barrier elements that prevent gene silencing in centrochromatin would thus help to optimize transgenesis using HAC vectors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-013-1362-9) contains supplementary material, which is available to authorized users

Generation of Trophoblast Stem Cells from Rabbit Embryonic Stem Cells with BMP4

Trophoblast stem (TS) cells are ideal models to investigate trophectoderm differentiation and placental development. Herein, we describe the derivation of rabbit trophoblast stem cells from embryonic stem (ES) cells. Rabbit ES cells generated in our laboratory were induced to differentiate in the presence of BMP4 and TS-like cell colonies were isolated and expanded. These cells expressed the molecular markers of mouse TS cells, were able to invade, give rise to derivatives of TS cells, and chimerize placental tissues when injected into blastocysts. The rabbit TS-like cells maintained self-renewal in culture medium with serum but without growth factors or feeder cells, whilst their proliferation and identity were compromised by inhibitors of FGFs and TGF-β receptors. Taken together, our study demonstrated the derivation of rabbit TS cells and suggested the essential roles of FGF and TGF-β signalings in maintenance of rabbit TS cell self-renewal

BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin

Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast

Hypertension control during the COVID-19 pandemic: results of the MMM2021 in Russia

Repetitive quarantines and social restrictions during the coronavirus disease 2019 (COVID-19) pandemic have negatively affected the population health in general, and the control of hypertension (HTN) in particular.Aim. To evaluate the control of HTN in the Russian population during the COVID-19 period based on the results of screening for HTN May Measurement Month 2021 (MMM2021).Material and methods. During May-August 2021, 2491 participants from 11 Russian regions took part in the screening. Participation was voluntary without restrictions on sex. All participants were over 18 years of age. During the screening, blood pressure (BP) was measured three times using automatic and mechanical BP monitors. In addition, a questionnaire was filled out on behavioral risk factors, comorbidities and therapy. HTN was diagnosed with systolic BP ≥140 mmHg and/ or diastolic blood pressure ≥90 mmHg and/or taking antihypertensive therapy. The questionnaire included questions about prior COVID-19, vaccinations and their impact on the intake of antihypertensive drugs.Results. The analysis included data from 2461 respondents aged 18 to 92, of which 963 were men (39,1%). The proportion of hypertensive patients was 41,0%, while among them 59,0% took antihypertensives and 30,9% were effectively treated. In comparison with pre-pandemic period according to MMM2018-2019, the higher proportion of HTN patients in the Russian sample was revealed during MMM2021 (41,0% vs 31,3%, p<0,001) with a comparable proportion of patients receiving antihypertensive therapy (60,7% vs 59,0%, p=0,05) and treatment efficacy (28,7% vs 30,9%, p=0,36). Monotherapy was received in 44,7% of cases, while dual and triple combination therapy — in 30,9% and 14,1%, respectively. The majority of respondents (~90%) did not adjust their antihypertensive therapy during the COVID-19 pandemic.Conclusion. According to HTN screening in Russia, there is persistent ineffective control of HTN, which may be due to both the worsening pattern of behavioral risk factors, limited access to healthcare during COVID-19, and the inertia of physicians and low adherence of patients due to the asymptomatic HTN course in the majority

Incorporation of Lysyl-tRNA Synthetase into Human Immunodeficiency Virus Type 1

During human immunodeficiency virus type 1 (HIV-1) assembly, tRNA(Lys) isoacceptors are selectively incorporated into virions and tRNA [Formula: see text] is used as the primer for reverse transcription. We show herein that the tRNA(Lys)-binding protein, lysyl-tRNA synthetase (LysRS), is also selectively packaged into HIV-1. The viral precursor protein Pr55(gag) alone will package LysRS into Pr55(gag) particles, independently of tRNA(Lys). With the additional presence of the viral precursor protein Pr160(gag-pol), tRNA(Lys) and LysRS are both packaged into the particle. While the predominant cytoplasmic LysRS has an apparent M(r) of 70,000, viral LysRS associated with tRNA(Lys) packaging is shorter, with an apparent M(r) of 63,000. The truncation occurs independently of viral protease and might be required to facilitate interactions involved in the selective packaging and genomic placement of primer tRNA [Formula: see text]

May Measurement Month 2019: adherence to treatment and hypertension control in Russia

The International Society of Hypertension and the World Hypertension League initiated a blood pressure screening study called May Measurement Month 2019 (MMM19) to improve the detection of elevated blood pressure (BP) and to assess BP control in patients with hypertension (HTN).Aim. To assess adherence to treatment of the hypertensive population according to MMM19 campaign in Russia.Material and methods. During May 2019, 5394 people from 21 regions of Russia took part in the screening. Participation was voluntary and did not imply gender restrictions; all subjects were over 18 years of age. During the screening, BP was measured three times using electronic and mechanical sphygmomanometers, as well as a questionnaire on the diabetes, history of cardiovascular events, smoking, and alcohol consumption was filled. Information was also collected on the date of last BP check and the administration of statins, acetylsalicylic acid and antihypertensive drugs. Data on height and body weight was obtained from respondents.Results. The analysis included data from 5274 participants aged 18 to 96 years (men — 1834 (34,8%)). Median age was 25 years, quartiles — 20 and 49 years. According to MMM19 data, the proportion of HTN patients in the Russian population was 31,9%, and with the exception of participants under 25 years old — 51,5%. Patients with HTN over 25 years old take antihypertensive therapy in 73,6%; 38,6% are characterized by irregular drug intake. Only 11,8% of men and 17,2% of women reach the target blood pressure <130/80 mm Hg. Only 20-30% of patients who used 4-5 antihypertensives reached the target BP level.Conclusion. According to MMM19 in Russia, only a third of high-risk patients measured BP over the past 12 months. There is also low adherence to antihypertensive therapy and inadequate control of HTN. Patients with HTN and a history of cardiovascular events are more likely to take antihypertensives regularly