Aim: To assess the safety and efficiency of H.E.L.P.-apheresis and cascade lipid-filtration in the treatment of severe lipid disorders in high-risk patients.

Methods: From 2016 to 2018 we observed 6 patients hyperLDLemia and high Lp(a)emia (> 60 mg/dL). The first group with H.E.L.P.-apheresis (n = 74 sessions) included 3 patients who underwent revascularization (coronary, femoral arteries). In the second group with cascade lipid-filtration (n = 92 sessions) - one patients underwent revascularization, two patients received drug therapy. Despite the lipid-lowering conventional therapy, no targeted low density lipoprotein (LDL) was obtained.

Results: The patients of the 1st group had threefold decrease of LDL, in patients of the 2nd group LDL decreased by 68%. At the same time, in both groups, we noted a decrease in Lp(a) after the procedure by 65%-68%. Despite a decrease in high density lipoprotein (by 22%-29%) after lipid apheresis procedures, there was a positive trend in apoB100/apoA index (a decrease of 33% after HELP-apheresis procedures and 60% after cascade lipid-filtration) and a decrease in atherogenic index (38% and 53%, respectively). The changes in hematological and haemostatic parameters remained within physiological intervals.

Conclusion: We noticed the successful application of lipid apheresis in patients with multifocal atherosclerosis and its complications.

Circulating monocytes are recruited to tissues, where they differentiate to macrophages and take part in the inflammation process or tissue remodeling. According to the traditional concept, macrophages are classified into pro-inflammatory (M1), non-activated (M0) or anti-inflammatory (M2) subsets that play distinct roles in the initiation and resolution of inflammation. This heterogeneity exists already at the monocyte level since monocytes can also belong to pro- or anti-inflammatory phenotypes. Growth factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and M-CSF play a principal role in their activation: GM-CSF drives the differentiation of “pro-inflammatory” monocytes to M1 macrophages, while M-CSF regulates differentiation of the “anti-inflammatory” subset of monocytes to M0 macrophages that have M2-like phenotypic and functional properties. More recent experimental findings led to a substantial update of monocyte-macrophage nomenclature to include the nature of the polarizing signal. In response to pro-inflammatory stimuli, monocytes can be directly polarized into 3 subsets of macrophages with the pro-inflammatory M1-like phenotype; with macrophages induced by interferon-γ having the strongest pro-inflammatory properties. When exposed to various anti-inflammatory stimuli, monocytes can differentiate to at least 5 subsets of M2-like macrophages. Of those, a subset generated under exposure to IL-4 (IL-13) has the most typical M2-like characteristics. Both in humans and in mice, monocyte-to-macrophage differentiation involves global transcriptome changes that are tightly controlled by various transcriptional regulators and signaling mechanisms. In this review, we discuss monocyte-macrophage heterogeneity and signaling pathways regulating the differentiation at transcription level.

During pregnancy, physiologic hormonal changes provoke a significant increase in triglyceride levels. Genetic abnormalities of triglyceride metabolism and secondary factors may multiply the risk of severe lipid abnormalities. Although severe gestational hypertriglyceridemia can be a life-threatening condition for both mother and fetus, its optimal treatment has not been fully clarified. A 33-year-old woman at 37 weeks of her second pregnancy was admitted to our clinic. Her triglyceride level was 57.8 mmol/L. Abdominal pain, nausea, vomiting or any other complaints were not reported. She kept a fat-restricted diet, however her triglyceride level remained 41 mmol/L. Therefore we decided to perform plasmapheresis with a replacement of human albumin as a colloidal solution. Complications did not occur during the treatment. Plasmapheresis reduced her triglyceride level by 54.1% (to 18.8 mmol/L), and the patient delivered a healthy female neonate at 40 weeks. In case of significantly increased values, plasmapheresis is a fast, effective and safe method for decreasing triglyceride level even in the third trimester.

Type 2 diabetes mellitus characterized by chronic hyperglycaemia is caused by insulin resistance and β-cell dysfunction. Glycogen accumulation, due to impaired metabolism, contributes to this “glucotoxicity” via dysregulated biochemical pathways promoting β-cell dysfunction. Thus, long-term exposition of insulin-secreted cells or isolated islets together with increased free fatty acids (FFA) and glucose levels can cause insulin-induced glucose secretion depression, damage to insulin gene expression and apoptotic death of cells. It is known that, the main regulator of pancreatic β-cells functioning and regulator of insulin gene expression, synthesis and secretion of insulin is glucose. Glucose enters cells and progressively metabolizes, in particular, to pyruvate in a cycle of tricarboxylic acids, subjected to oxidative phosphorylation, during which formed adenosine triphosphate and reactive oxygen radicals (ROS). Although, when more glucose enters the cell, there are other ways in which extra glucose can be transferred to reserve and of the glucose molecules can form ROS. The release of excessive amounts of FFA leads to lipotoxicity, as lipids and metabolites produce ROS in the endoplasmic reticulum and mitochondria. This affects both adipose and non-fat tissue, making up its pathophysiology in many organs. This overview demonstrates that the insulin gene is expressed in pancreatic β-cells. Glucose is the main physiological regulator of insulin gene expression. It controls the effect of transcription factors, insulin mRNA stability, and transcription rate. Glucolipotoxicity mechanisms affect the transcription factors MafA and PDX-1. Important is the β-cells damaging, which is connected with the oxidative stress and the synthesis of ceramides.

Aim: Cardiac angina is a disease in which discomfort or retrosternal pain may occur. Atherosclerosis of coronary arteries is one of the main risk factors for cardiac angina. The aim of the investigation was to analyze the association of 11 mitochondrial genome mutations with cardiac angina. In our preliminary studies an association of these mutations with atherosclerosis, a risk factor for cardiac angina, was found.

Methods: We used samples of white blood cells collected from 192 patients with cardiac angina and 201 conventionally healthy study participants. DNA from blood leukocyte samples was isolated using a phenol-chloroform method. DNA amplicons containing the investigated regions of 11 mitochondrial genome mutations (m.12315G>A, m.652delG, m.5178C>A, m.14459G>A, m.3336T>C, 652insG, m.3256C>T, m.1555A>G, m.15059G>A, m.13513G>A, m.14846G>A) were pyrosequenced. The heteroplasmy level of mitochondrial DNA (mtDNA) mutations was analyzed using a method developed by our laboratory on the basis of pyrosequencing technology.

Results: According to the obtained data, three mitochondrial mutations of human genome correlated with cardiac angina. A positive correlation was observed for mutation m.14459G>A (P ≤ 0.05). One single nucleotide substitution m.5178C>A (P ≤ 0.1) had a trend for positive correlation. A negative correlation for mutation m.15059G>A with cardiac angina (P ≤ 0.05) was found.

Conclusion: MtDNA mutations m.14459G>A and m.5178C>A can be used for evaluation the predisposition of individuals to atherosclerotic lesions. At the same time, mitochondrial genome mutation m.15059G>A may be used for gene therapy of atherosclerosis.

Lipid accumulation in cells of subendothelial intima and the formation of foam cells is the earliest and the most noticeable manifestation of atherosclerosis at the cellular level. Generally, the foam cell formation is the result of interaction of cell with pro-atherogenic low-density lipoprotein providing cholesterol delivery and anti-atherogenic high-density lipoprotein providing its efflux. In this review, we discuss possible mechanisms of foam cell formation, the role of intracellular lipid deposition as a trigger of atherosclerotic lesion development, current approaches to diagnostics and strategies for preventing atherosclerosis based on recent knowledge of causes of foam cell formation.

Carotid artery atherosclerosis or stenosis is frequently present at the carotid bifurcation or the internal carotid artery, accounting for at least 20% of all ischemic strokes. High levels of serum total cholesterol and low-density lipoprotein cholesterol are established risk factors for genesis and progression of atherosclerotic lesions through various mechanisms. In addition, accumulating evidence has shown that a high level of triglyceride is associated with increased atherosclerosis risks. The so-called “vulnerable plaque” with a large lipid core, thin fibrous cap and intra-plaque hemorrhage tends to cause subsequent thromboembolic ischemic events. Statins are known not only to lower serum cholesterol levels but also to promote plaque stabilization via pleiotropic effects such as reducing subclinical systemic inflammation, endothelial activation, leukocyte intra-plaque infiltration, and increasing intimal smooth muscle cell migration. This article discusses the mechanisms of atherosclerosis formation induced by dyslipidemia and the role of lipid-lowering agents including statins in patients with symptomatic and asymptomatic atherosclerotic carotid artery stenosis.

High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport (RCT) but also exhibits, anti-inflammatory, endothelial/vasodilatory, anti-thrombotic, antioxidant, anti-aggregating, anticoagulant and cytoprotective functions, which enhance its protective effect against cardiovascular disease. However, the function of HDL is dependent upon genetic, environmental and lifestyle factors. Modification of the protein or lipid components of HDL in certain conditions may convert the HDL particles from anti-inflammatory to pro-inflammatory and pro-atherogenic by limiting their ability to promote RCT and to prevent LDL modification. In our review, we will present the clinical and scientific data pertaining to the factors and conditions that impair HDL functionality and we will discuss the effects of dysfunctional HDL on atherogenesis.