iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.

Defects in the low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. LDLR deficiency in hepatocytes leads to elevated blood cholesterol levels, which damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully understood.

Calling and Phasing of Single-Nucleotide and Structural Variants of the Gene Using Oxford Nanopore MinION.

The locus has clinical significance for lipid metabolism, Mendelian familial hypercholesterolemia (FH), and common lipid metabolism-related diseases (coronary artery disease and Alzheimer's disease), but its intronic and structural variants are underinvestigated. The aim of this study was to design and validate a method for nearly complete sequencing of the gene using long-read Oxford Nanopore sequencing technology (ONT). Five PCR amplicons from of three patients with compound heterozygous FH were analyzed.

Induced pluripotent stem cell line ICGi037-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to heterozygous p.Trp443Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder increasing premature cardiovascular diseases risk due to atherosclerosis. Pathogenic mutations in the LDLR gene cause most FH cases. Available treatments are effective not for all LDLR mutations.

Induced pluripotent stem cell line ICGi038-A, obtained by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia due to compound heterozygous c.1246C > T/c.940 + 3_940 + 6del mutations in LDLR.

The development of cellular models for familial hypercholesterolemia (FH) is an important direction for creating new approaches to atherosclerosis treatment. Pathogenic mutations in the LDLR gene are the main FH source. We generated an iPSC line from peripheral blood mononuclear cells of the patient with compound heterozygous c.

Information Conversion in Measuring Channels with Optoelectronic Sensors.

The purpose of this work is the authors' attempt to identify the main phases of information transformation in measurement channels on the example of an optical measurement channel with microprocessor control. The authors include such phases: hardware implementation and analytical representation of an optical sensor's converting functions and a current-to-voltage converter; based on the methods of experimental computer science, the converting functions and sensitivity are deduced, analytical dependences for estimation of a range of measurement are obtained. It is shown that the choice of information transmission type in the microprocessor measuring channel significantly affects the speed of the measuring channel.

Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR.

Familial hypercholesterolemia (FH) is a monogenic disease, leading to atherosclerosis due to a high level of low-density lipoprotein cholesterol. Most cases of the disease are based on pathological variants in the LDLR gene. Hepatocyte-like and endothelial cells derived from individual iPSCs are a good model for developing new approaches to therapy.

The , , and Variants of Index Patients with Familial Hypercholesterolemia in Russia.

Familial hypercholesterolemia (FH) is a common autosomal codominant disorder, characterized by elevated low-density lipoprotein cholesterol levels causing premature atherosclerotic cardiovascular disease. About 2900 variants of , , and genes potentially associated with FH have been described earlier. Nevertheless, the genetics of FH in a Russian population is poorly understood.

[Lipolysis in very low density lipoproteins - locus minoris resistentiae - in the pathogenesis of hypertriglyceridemia. Positive effects of diet, polyenic fatty acids, statins and fibrates.].

Inhibition of hydrolysis of palmitic and oleic triglycedires (TG) in very low density lipoproteins (VLDL), slow formation of active apoВ-100 conformation, blockade of апоЕ/В-100 ligand formation in VLDL and their reduced uptake by insulin-dependent cells cause hypertriglyceridemia (HTG). Palmitic and oleic VLDL (>80% total VLDL) are not converted in low density lipoproteins (LDL). Atherosclerosis is not an alimentary deficiency of polyenic fatty acids (PFA), but results from low in vivo bioavailability of PFA in LDL against the background of high dietary palmitic FA and palmitic LDL.

The association of lipoprotein(a) and apolipoprotein(a) phenotypes with peripheral artery disease.

Aim: Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and myocardial infarction. Data about the role of Lp(a) in the development of peripheral artery disease (PAD) is controversial and uncertain. The aim of the study was to evaluate the association between Lp(a), apolipoprotein(a) [apo(a)] phenotypes and PAD.

[Giant Aneurysms in Coronary Arteries of a Young Woman].

Coronary arteries aneurysms with their thrombotic occlusion are known to be detected in young patients who have suffered Kawasaki disease in childhood. The other vascular beds are usually not involved. In the literature one can find not enough information regarding diagnostics of this pathology, as well as no specific treatment algorithm.

[Recommendations of the European Society of Cardiology and the European Atherosclerosis Society on Cardiovascular Disease Prevention and Management of Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment (2016): Basic S.G.].

This review summarizes the main provisions of the new, issued in 2016, recommendations of the European Society of Cardiology and Atherosclerosis Society in cooperation with the European Association on Cardiovascular Prevention and Rehabilitation on Cardiovascular disease prevention and Management of dyslipidemia. In these recommendations, the following trends can be traced distinctly: priority in primary prevention is given to non-drug methods of influence; targets of hypolipidemic therapy are identified not only for low density lipoprotein (LDL) cholesterol (CH), but also for non-high density lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In the field of therapy, in which statins remain the main tool of correction of hyperlipidemia, it is recommended to more widely resort to the use of combination therapy, especially in cases of familial hypercholesterolemia or intolerance to statins; introduction of a new class of drugs- inhibitors of proprotein convertase subtilisin/kexin type 9 makes it possible to further reduce the level of LDLCH, lipoprotein(a) more than 60%.

[Degenerative Aortic Stenosis: Modern View on Development, Course, and Management].

Degenerative aortic stenosis is an acquired heart defect manifesting as progressive thickening and calcification of leaflets of originally normal tricuspid or congenital bicuspid aortic valve with development of orifice narrowing, left ventricular hypertrophy, and high risk of cardiovascular complications. In this review we present modern concepts of formation and progression of degenerative aortic stenosis and discuss optimal methods of management of this disease.

[Vasorenal Hypertension and Primarily Contracted Kidney in a Man Aged 44 years: Is Invasive Intervention Needed?].

Presentation of a clinical case of vasorenal hypertension in a patient with chronic renal artery occlusion and primarily contracted kidney is accompanied by discussion of current recommendations concerning indications to invasive intervention in patients with vasorenal arterial hypertension.

[The integrated etiology and separate pathogenesis of atherosclerosis and atheromatosis. The differences of fatty acids transfer in lipoproteins of herbivorous and carnivorous animals.].

According phylogenetic theory of general pathology, overconsumption of meat food by herbivorous animals always results in atherosclerosis and atheromatosis of intima of arteries. The etiological factors of atherosclerosis, atheromatosis in vivo: a) absorption by cells of polyene fatty acids in anoB-100 lipoproteins of low density; b) impossibility of converting exogenous palmitic saturated fatty acids into mono-unsaturated oleic fatty acid; c) monocytes-macrophages in intima inactively hydrolyze polyene fatty acids esterified by alcohol cholesterol. The disorder of biological function of trophology (nutrition), biological reaction of exotrophy (external nutrition) and aphysiologically high content of palmitic unsaturated fatty acids and alcohol cholesterol in food become a pathogenic factors.

[The individual fatty acids of blood plasma: biological role of substrates, parameters of quantity and quality, diagnostic of atherosclerosis and atheromotosis.].

The atherosclerosis and atheromotosis are supposed to be, according to phylogenetic theory of general pathology, two etiologically different aphysiological processes, unified by community of pathogenesis. The atherosclerosis is a derangement of biological function of trophology (feeding), biological reaction of exotrophy (external feeding) and biological function of adaptation, biological reaction of compensation in response to deficiency of ῳ-3 and ῳ-6 polyenoic fatty acids. In case of deficiency of polyenoic fatty acids in cells and during synthesis of eicosanoids of group I from unsaturated endogenous ῳ-6 С20: 3 digomo-γ-linoleic unsaturated fatty acid, atherosclerosis is developed, a complex metabolism disorder in vivo.

[The physical chemical and biological features of triglycerides. The cell absorption of functionally different palmitic+oleic lipoproteins of very low and density and linoleic+linolenic lipoproteins of low density.].

The earlier insulin-independent low-density lipoproteins and more late insulin-dependent very low-density lipoproteins implement different functions at the stages of phylogenesis. The disorder of biological function of trophology, alteration of fatty acids in triglycerides, prevalence of palmitic very low-density lipoproteins over oleic very low-density lipoproteins supply mitochondria of cells with non-optimal substrate - palmitic saturated fatty acid for gaining energy, ATP synthesis. Physiologically, cells implement oleic alternative of fatty acids metabolism, oxidizing mainly ω-9 endogenous oleic mono-unsaturated fatty acid.

[The oleic triglycerides of palm oil and palmitic triglycerides of creamy fat. The reaction of palmitoylation, potassium and magnesium palmitate, absorption of fatty acids by enterocytes and microbiota of large intestine].

The decreasing of content of animal, palmitic milk fat (butter) by means of its substitution with vegetable, oleic, palmy oil in food of adults optimal by its quantity is physically chemically and biologically substantiated. In oleic palmy oil higher content of oleic mono unsaturated fatty acid and oleic triglycerides than in creamy fat is established. The biologic availability of palmitic unsaturated palmitic acid in the form of free fatty acid is decreased at its absorption by enterocytes of small intestines is detected.

[The evaluation of unsaturation of blood lipids using methods of physical chemistry and clinical biochemistry. The insulin regulation of metabolism of fatty acids, number of double binds and cell absorption of glucose].

It is supposed that the main cause of insulin synthesis at late stages of phylogenesis became discrepancy between increase in vivo need in energy and physical chemical parameters of palmitic saturated fatty acid; its transportation to cells in composition of lipoproteins in optimal quantity (more than 15% of all fatty acids) became in vivo unfeasible. The biological role of insulin consists in supporting of insulin-dependent cells (skeletal miocytes in the first place) with substrates for gaining energy. The hormone transforms all palmitic saturated fatty acid endogenously synthesized from glucose into specific for animal cells rn-9 C18:1 oleic mono unsaturated fatty acid.

[The positional specificity of individual triglycerides-substrates for lipase action. The oleic triglycerides of palm oil, palmitic triglycerides of milk, ions of calcium and magnesium.].

The counter-insulin effect of surplus of palmitic fatty acid in food is implemented under: a) formation in vivo of palmitic type of fatty acids metabolism with deficiency of substrate for ATP synthesis and permanent shortage of energy for accomplishment of biologic functions; b) compensatory activation of biologic function of adaptation, biologic reaction of compensation. The activation with catecholamines in visceral fatty cells of gland the hormone-dependent lipase which is not blocking insulin, increases content of unesterified fatty acids in blood plasma. Until in blood plasma the level of unesterified fatty acids is increased the cells phylogenetically justified stop absorption of glucose along with development of hyperglycemia and hypertriglyceridemia - insulin resistance syndrome.

Subclinical arterial wall damage in patients at low to moderate cardiovascular risk.

Aim: The aim of this paper is to study the degree of subclinical arterial wall damage in subjects at low and moderate risk of cardiovascular death by the SCORE scale using instrumental research methods.

Methods: We enrolled 600 patients (mean age 49.0 +/- 7.

[Mass spectrometry analysis of blood plasma lipidome as method of disease diagnostics, evuation of effectiveness and optimization of drug therapy].

A new method for the analysis of blood lipid based on direct mass spectrometry of lipophilic low molecular weight fraction of blood plasma has been considered. Such technique allows quantification of hundreds of various types of lipids and this changes existing concepts on diagnostics of lipid disorders and related diseases. The versatility and quickness of the method significantly simplify its wide use.

[Lipoprotein-associated phospholipase A2 serum levels in patients from different categories of cardiovascular risk].

Aim: To compare levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in blood serum of patients from different cardiovascular risk categories.

Material And Methods: Patients from Moscow prospective study database (n = 519) were divided into 4 cardiovascular risk categories according to present clinical recommendations (low, moderate, high, very high). Measurement of Lp-PLA2 concentration (mass) was performed using PLAC Test ELISA Kit.

Lipoprotein(a) level and apolipoprotein(a) phenotype as predictors of long-term cardiovascular outcomes after coronary artery bypass grafting.

Objective: To evaluate the relationships of lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a)) phenotype to major adverse cardiovascular events after coronary artery bypass grafting (CABG) in long-term follow-up.

Methods: This single-center study included 356 patients with stable coronary heart disease (CHD) who underwent successful CABG. At baseline, we assessed the patient's risk factor profile for atherosclerosis, Lp(a) concentration and apo(a) phenotype.

[Hypolipidemic and pleiotropic effects of a combination of simvastatin and ezetimibe in patients with different types of hyperlipidemia].

The review considers trials dealing with the efficiency of combination hypolipidemic therapy with simvastatin and ezetimibe. Its synergistic potentiating effect can cause a considerable decrease in the level of total cholesterol, low-density lipoproteins, triglycerides, and C-reactive protein, which are important participants in the atherogenic process. This effect promotes the achievement of hypolipidemic therapeutic goals in many cases when this cannot be attained by high-dose statin monotherapy.