Clinical case of myocardial infarction with unspecified familial hypercholesterolemia

Familial hypercholesterolemia is a hereditary autosomal dominant disease characterized by a violation of cholesterol metabolism. This nosology was first described in the late 1930s by the Norwegian clinician Karl Moeller, he proposed the idea that hypercholesterolemia and tendon xanthomas are associated with cardiovascular diseases through the inheritance of a single gene. In 1964, two clinical phenotypes of familial hypercholesterolemia were discovered: heterozygous and homozygous, associated with an unfavorable prognosis. To date, it is known that the long-running process of accumulation of low-density lipoproteins in the intima of blood vessels may not have clinical symptoms for many years due to the developed system of collaterals and the absence of hemodynamically significant stenosis. However, without timely diagnosis and appropriate therapy, this condition inevitably leads to the development of a cardiovascular event. The article presents a clinical case demonstrating the development of myocardial infarction in a patient with a late diagnosis of this disease.

Modern biomarkers of oxidative stress estimated by immuno-enzymal analysis

The literature review presents the results of studies carried out in the world over the past years, devoted to the study of factors and markers of oxidative stress in the development of therapeutic diseases, especially cardiovascular diseases. The article describes the results of studies using enzyme immunoassay of such biomarkers of oxidative stress as glutathione peroxidase, superoxide dismutase, oxidatively modified low density lipoproteins, carbonylated proteins, as well as the general antioxidant capacity of the blood.

Prevalence of hypercholesterolemia in young people under 45 years old with abdominal obesity in Novosibirsk

The study was devoted to the study of the prevalence of hypercholesterolemia (hyper-Chol) and hypercholesterolemia of low density lipoproteins (hyper-LDL-C) against the background of abdominal obesity (AO) in a population aged 25–44 years in Novosibirsk. Material and methods. A crosssectional survey of the population aged 25–44 years in Novosibirsk (Russia) was carried out. 1415 people were examined, including 670 men (47.3 %) and 745 women (52.7 %), pregnant women or being on maternity leave were not included in the study). All subjects were assessed for the presence of AO, hyper-Chol and hyper-LDL-C. Results. Individuals with AO had higher average values of total cholesterol and LDL cholesterol. The prevalence of hyper-Chol in individuals with AO was 1.3 times higher and hyper-LDL-C – 1.2 times higher than in individuals without AO. In women with AO, the prevalence of hyper-Chol was 1.2 times higher and hyper-LDL-C – 1.3 times higher than in women without AO. In men with AO, the prevalence of hyper-Chol was 1.4 times higher and hyper-LDL-C – 1.2 times higher than in men without AO. When conducting logistic regression analysis, it was found that in a young population under 45 years of age, abdominal obesity was significantly associated with the presence of atherogenic hypercholesterolemia in both sexes. In men, significant associations of AO with both hyper-Chol and hyper-LDL-C were noted, in women – only with hyper-LDL-C. Conclusions. A population study of young people (25–44 years old) revealed associations of atherogenic hypercholesterolemia with abdominal obesity.

Prevalence and factors associated with hypertension among adults with and without HIV in Western Kenya

Introduction The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. Methods In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. Results Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p<0.002). In multivariate analyses, persons with HIV were 37% less likely to have hypertension compared to HIV-negative individuals (adjusted prevalence ratio 0.63; 95% confidence interval: 0.46–0.86). Other factors that were associated with hypertension in all participants included older age >40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. Conclusion Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

Native and Oxidized Low-Density Lipoproteins Increase the Expression of the LDL Receptor and the LOX-1 Receptor, Respectively, in Arterial Endothelial Cells

Atherosclerotic artery disease is the major cause of death and an immense burden on healthcare systems worldwide. The formation of atherosclerotic plaques is promoted by high levels of low-density lipoproteins (LDL) in the blood, especially in the oxidized form. Circulating LDL is taken up by conventional and non-classical endothelial cell receptors and deposited in the vessel wall. The exact mechanism of LDL interaction with vascular endothelial cells is not fully understood. Moreover, it appears to depend on the type and location of the vessel affected and the receptor involved. Here, we analyze how native LDL (nLDL) and oxidized LDL (oxLDL) modulate the expression of their receptors—classical LDLR and alternative LOX-1—in endothelial cells derived from human umbilical artery (HUAECs), used as an example of a medium-sized vessel, which is typically affected by atherosclerosis. Exposure of HUAECs to nLDL resulted in moderate nLDL uptake and gradual increase in LDLR, but not LOX-1, expression over 24 h. Conversely, exposure of HUAECs to oxLDL, led to significant accumulation of oxLDL and rapid induction of LOX-1, but not LDLR, within 7 h. These activation processes were associated with phosphorylation of protein kinases ERK1/2 and p38, followed by activation of the transcription factor AP-1 and its binding to the promoters of the respective receptor genes. Both nLDL-induced LDLR mRNA expression and oxLDL-induced LOX-1 mRNA expression were abolished by blocking ERK1/2, p-38 or AP-1. In addition, oxLDL, but not nLDL, was capable of inducing LOX-1 through the NF-κB-controlled pathway. These observations indicate that in arterial endothelial cells nLDL and oxLDL signal mainly via LDLR and LOX-1 receptors, respectively, and engage ERK1/2 and p38 kinases, and AP-1, as well as NF-κB transcription factors to exert feed-forward regulation and increase the expression of these receptors, which may perpetuate endothelial dysfunction in atherosclerosis.

STUDY OF THE EFFECT OF CHITOSAN EXTRACTED FROM THE MUSHROOM ON THE EXPERIMENTALLY INDUCED HYPERLIPIDEMIA IN MALE RABBITS

The present study aimed to identify the therapeutic evaluation of chitosan extracted from the fungus cushroom and pure chitosan on glucose and lipid profile in the blood of 35 male rabbits with hyperlipidemia induced experimentally by cholesterol. The tests included estimation of glucose levels, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins. hyperlipidemia was induced in the male rabbits used in the study which was administered orally with cholesterol 150mg/kg body weight for a week. rabbits were divided into seven groups: control, cholesterol, pure chitosan, mushroom chitosan, cholesterol and pure chitosan, cholesterol and mushroom chitosan and cholesterol and simvastatin. The results of the study showed, the hyperlipidemia induced experimentally resulted a significant increase (P<0.05) in TC, TG, LDL, and VLDL, while no significant difference in HDL compared with control group, on the otherwise the glucose level significantly increase than control. Also, groups of animals treatment with pure chitosan and mushroom chitosan showed a significant decrease (P<0.05) in glucose, TC, TG, LDL, and VLDL, and no significant difference in HDL compared with control group. While, the groups showed treatment with cholesterol and pure chitosan, cholesterol and mushroom chitosan, cholesterol and simvastatin a significant decrease (P<0.05) in glucose, TC, TG, LDL, and VLDL, and a significant increase (P<0.05) in HDL compared with the cholesterol group. The research study revealed that chitosan extracted from mushroom can control the levels of fat concentrations and their complications, in addition to its important role in biochemical variables, and treatment of most disease cases, especially cardiovascular disease.

Association between Dyslipidemia and Vitamin D Deficiency: a Cross-Sectional Study

Introduction: Dyslipidemia is one of the most common metabolic disorders. Vitamin D is one of the essential fat soluble vitamins which has many functions in the human body. Aim: The aim of this study was to evaluate the association between dyslipidemia and vitamin D deficiency. Materials and methods: This is a cross-sectional study which included 130 participants (58 males and 72 females) aged between 20-70 years and conducted between June 1 and October 30, 2020. The level of vitamin D was determined for each participant; we also measured the serum levels of cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein. Results: There were 79 persons with vitamin D deficiency, 21 persons were vitamin D insufficient, and 10 - vitamin D sufficient. There were significant differences in the level of cholesterol, triglycerides, high-density and low-density lipoproteins according to the level of vitamin D. Conclusions: Deficiency of vitamin D has a negative impact on the levels of cholesterol, triglycerides, high-density and low-density lipoproteins.

HDLs extract lipophilic drugs from cells

High-density lipoproteins (HDLs) prevent cell death induced by a variety of cytotoxic drugs. The underlying mechanisms are however still poorly understood. Here we present evidence that HDLs efficiently protect cells against thapsigargin (TG), a sarco/ endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) inhibitor, by extracting the drug from cells. Drug efflux could also be triggered to some extent by low-density lipoproteins and serum. HDLs did not reverse the non-lethal mild ER stress response induced by low TG concentrations or by SERCA knock-down but HDLs inhibited the toxic SERCA-independent effects mediated by high TG concentrations. HDLs could extract other lipophilic compounds, but not hydrophilic substances This work shows that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. This can be beneficial if lipophilic xenobiotics are toxic but may be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide.

The Correlation between Extracellular Heat Shock Protein 70 and Lipid Metabolism in a Ruminant Model

Metabolic stress in early lactation cows is characterized by lipolysis, ketogenesis, insulin resistance and inflammation because of negative energy balance and increased use of lipids for energy needs. In this study the relationship between lipid metabolite, lipid-based insulin resistance, and hepatocyte functionality indexes and tumor necrosis factor alpha (TNF-α) with extracellular heat shock protein 70 (eHsp70) was investigated. The experiment included 50 cows and all parameters were measured in blood serum. In cows with a more pronounced negative energy balance, the following was determined: a higher concentration of eHsp70, TNF-α, non-esterified fatty acid (NEFA), beta-hydroxybutyrate (BHB), NEFA to insulin and NEFA to cholesterol ratio and lower concentration of cholesterol, very low-density lipoproteins (VLDL), low density lipoproteins (LDL) and liver functionality index (LFI). The eHsp70 correlated negatively with the values of cholesterol, VLDL, LDL, and triglycerides, while correlated positively with the level of NEFA and BHB. A higher concentration of eHsp70 suggests the development of fatty liver (due to a higher NEFA to cholesterol ratio and lower LFI) and insulin resistance (due to a lower revised quantitative insulin sensitivity check index RQUICKI-BHB and higher NEFA to insulin ratio). The eHsp70 correlated positively with TNF-α. Both TNF-α and eHsp70 correlated similarly to lipid metabolites. In cows with high eHsp70 and TNF-α values we found higher concentrations of NEFA, BHB, NEFA to insulin and NEFA to cholesterol ratio and a lower concentration of triglycerides and VLDL cholesterol compared to cows that had only high TNF-α values. Based on the positive correlation between eHsp70 and TNF-α, their similar relations, and the additional effect of eHsp70 (high TNF-α + eHsp70 values) on lipid metabolites we conclude that eHsp70 has pro-inflammatory effects implicating lipolysis, fatty liver, and fat tissue insulin resistance.

Caveolae mediated endocytosis of VLDL particles in macrophages requires NPC1 and STARD3 for further lysosomal processing

Macrophages accumulate triglycerides under certain pathological conditions such as atherosclerosis. Triglycerides are carried in the bloodstream as part of very low-density lipoproteins (VLDL) and chylomicrons. How macrophages take up and process VLDL-lipids is not very well known. Here, using VLDL-sized triglyceride-rich emulsion particles, we aimed to study the mechanism by which VLDL-triglycerides are taken up, processed, and stored in macrophages. Our results show that macrophage uptake of emulsion particles mimicking VLDL (VLDLm) is dependent on lipoproteins lipase (LPL) and requires the lipoprotein-binding C-terminal domain of LPL but not the catalytic N-terminal domain. Subsequent internalization of VLDLm-triglycerides by macrophages is carried out by caveolae-mediated endocytosis, followed by triglyceride hydrolysis catalyzed by lysosomal acid lipase. Transfer of lysosomal fatty acids to the ER for subsequent storage as triglycerides is mediated by Stard3, whereas NPC1 was found to promote the extracellular efflux of fatty acids from lysosomes. Our data provide novel insights into how macrophages process VLDL-derived triglycerides and suggest that macrophages have the remarkable capacity to excrete part of the internalized triglycerides as fatty acids.