Atherogenic Serum Research Articles

The Association of Blood Serum Atherogenicity with Risk Factors for Cardiovascular Disease

The Association of Blood Serum Atherogenicity with Risk Factors for Cardiovascular Disease

Hepatokines Orosomucoid: Pathogenetic Role in Liver Steatosis

The liver is an endocrine organ because hepatocytes produce a number of biologically active regulators of systemic metabolism and energy balance – hepatokines, which include orosomucoids (seromucoids). According literuture data, orosomucoids reduce the production of activated oxygen forms, protect adipose tissue, regulate immune processes, act as cardioprotectors, and drug carriers. Orosomucoids production is associated with the development of fatty hepatosis too but pathogrenetic role of orosomucoids in liver steatosis needs more investigations. The objective: to evaluate the effects of orosomucoids on systemic metabolism in patients with coronary artery disease with comorbid liver steatosis. Materials and methods. In 104 patients with coronary artery disease, unstable angina the content of orosomucoids was additionally determined by the unified orcin’s method (normal value 0,13–0,23 units). Patients were investigated according modern quidelines and Helsinki declaration of human rights. According liver steatosis presentce patients were divided into two statistically equal groups with comorbid liver steatosis (n=87; 83,65%) and intact liver (n=17; 16,35%). The results were calculated statistically with p<0.05 level. Results. Patients with and without hepatic steatosis had identically elevated orosomucoids levels (0,38±0,02 vs 0,40±0,05 units; p>0.05), but their correlations were different. The level of orosomucoids correlated directly with the duration of inpatient treatment, heart rate, acute-phase indicators of inflammation, fasting blood glucose and prothrombin time, and was conversely associated with total cholesterol and low-density lipoproteins, prothrombin index (all p<0.05). Conclusions. Orosomucoid hepatokines are key regulators of lipogenesis, under conditions of liver steatosis in patients with coronary artery disease, unstable angina, their growth correlates with activation of cellular and serum markers of inflammation, reduction of serum atherogenicity, glucose intolerance, and hypocoagulation.

Differences in Chronic Low-Grade Inflammation and Metabolic Disturbances between VDR Genotypes in an Ethnically Homogenous Postmenopausal Female Population from Poland.

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50-60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

A Metabolic Enhancer Protects against Diet-Induced Obesity and Liver Steatosis and Corrects a Pro-Atherogenic Serum Profile in Mice.

Metabolic Syndrome (MetS) affects hundreds of millions of individuals and constitutes a major cause of morbidity and mortality worldwide. Obesity is believed to be at the core of metabolic abnormalities associated with MetS, including dyslipidemia, insulin resistance, fatty liver disease and vascular dysfunction. Although previous studies demonstrate a diverse array of naturally occurring antioxidants that attenuate several manifestations of MetS, little is known about the (i) combined effect of these compounds on hepatic health and (ii) molecular mechanisms responsible for their effect. We explored the impact of a metabolic enhancer (ME), consisting of 7 naturally occurring antioxidants and mitochondrial enhancing agents, on diet-induced obesity, hepatic steatosis and atherogenic serum profile in mice. Here we show that a diet-based ME supplementation and exercise have similar beneficial effects on adiposity and hepatic steatosis in mice. Mechanistically, ME reduced hepatic ER stress, fibrosis, apoptosis, and inflammation, thereby improving overall liver health. Furthermore, we demonstrated that ME improved HFD-induced pro-atherogenic serum profile in mice, similar to exercise. The protective effects of ME were reduced in proprotein convertase subtilisin/kexin 9 (PCSK9) knock out mice, suggesting that ME exerts it protective effect partly in a PCSK9-dependent manner. Our findings suggest that components of the ME have a positive, protective effect on obesity, hepatic steatosis and cardiovascular risk and that they show similar effects as exercise training.

Association of atherogenic serum lipids and platelet activation with changes in arterial stiffness in patients with type 2 diabetes

Association of atherogenic serum lipids and platelet activation with changes in arterial stiffness in patients with type 2 diabetes

The beneficial effects of virgin olive oil against oxidative stress induced by hypercholesterolemia in rats

Cardiovascular disease (CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects. This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard food and receiving by gavage virgin olive oil (HCD+VOO) and (4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), Low–Density Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in High–Density Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.

High Serum Atherogenicity and the Risk of Developing Type 2 Diabetes Mellitus

BackgroundEvidence sustained that lipid disorders may increase the risk of developing type 2 diabetes mellitus and its cardiovascular complications. Objective: The purpose of the study was to establish the correlation between lipid changes and atherogenic index in diabetes patients and to evaluate its utility as risk predictor. MethodsThe research was done on 69 senescent patients: 41 diabetes mellitus vs. 28 healthy control patients. Serum atherogenicity was assessed by atherogenic index, computed as log (TG/HDL), and the atherogenic risk was estimated in 3 categories: low, medium and high. ResultsData revealed an increase of triglycerides, cholesterol, LDL-cholesterol, non-HDL-cholesterol and a decrease of HDL-cholesterol at diabetes patients vs. control. Also, we noticed a significant increase of atherogenic index (p<0.0001) in diabetes patients vs. control. Prevalence of dyslipidemia at diabetes patients increased from 28.57% in the low risk atherogenic index group to 73.91% in the high risk atherogenic index group. Linear regression equation revealed that non-HDL-cholesterol is positively correlated with glucose (p<0.05) and atherogenic index (p<0.0001). Diagnostic test evaluation for atherogenic index indicated: 72.79% assay accuracy, 82.93% sensitivity, 57.14% specificity and relative risk estimate=2.42. Multivariate logistic regression analysis showed that patients with high atherogenic index had 6.47-fold risk for diabetes [OR 6.47, 95% CI: 2.14-19.56; p=0.0009]. Conclusion: Besides routine lipid panels, as alternative method to assess dyslipidemia, diabetes and its cardiovascular events, atherogenic index should be used as a good risk predictor. Also, non-HDL-cholesterol should be taking into account in guidelines and management of diabetes.

Blood serum atherogenicity in patients with systemic lupus erythematosus

Background and Aims: Patients with systemic lupus erythematosus (SLE) are at high risk of atherosclerosis development. Serum atherogenicity, the ability of blood serum to induce intracellular cholesterol accumulation in cultured cells is a potential marker for cardiovascular risk assessment. The aim of this study was to estimate the association of serum atherogenicity of SLE patients with disease activity and corticosteroids (CS) administration.

Serum-induced cholesterol accumulation in cultured blood-derived monocytes as a marker of atherosclerosis

Background and Aims: The ability of human serum to induce accumulation of intracellular cholesterol in cultured cells was described as a phenomenon of blood serum atherogenicity. The present study was performed to assess a potential role of serum atherogenicity in prognosis of atherosclerosis development.

MO838PARAOXONASE 1 GENE POLYMORPHISMS CONCERNING CARDIOVASCULAR MORTALITY IN CIGARETTE SMOKERS AND NON-SMOKERS TREATED WITH HEMODIALYSIS

Abstract Background and Aims Paraoxonase 1 gene (PON1) single nucleotide variants (SNVs), known as associated with lipoprotein peroxidation, are related to atherosclerotic diseases, including coronary heart disease (CHD). Cigarette smoking, causing increased susceptibility to lipoprotein oxidation, contributes to cardiovascular events, and its effects are linked with PON1 SNVs. We investigated the association of PON1 rs705379 (-108C&amp;gt;T), rs854560 (163A&amp;gt;T), and rs662 (575A&amp;gt;G) SNVs with cardiovascular mortality in maintenance hemodialysis (HD) patients concerning cigarette smoking status. Method In the HD group, there were 206 smokers and 659 non-smokers. Among all patients who died (n = 542), cardiovascular mortality was similar in smokers and non-smokers (59.0% vs. 59.3%, respectively). Deceased smokers were burning 20 (5 - 25) cigarettes daily. We obtained PON1 polymorphisms by HRM analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). All cardiovascular, cardiac, CHD- and non-CHD-related deaths were analyzed in smokers and non-smokers concerning PON1 SNVs and DM status. The Kaplan-Meier method with the log-rank test and the Cox regression analyses were applied for the estimation of survival. If computed P-values were below 0.05, the adjustment for sex, age, and HDL-cholesterol was applied. We have shown only adjusted P-values for survival analyses. Results HD cigarette smokers, who died from cardiovascular diseases, were younger (63.5, 31.1 – 86.3 vs. 74.0, 26.8 – 95.9 years, P = 2.992e-10), predominantly men (70, 85.3% vs. 91, 38.1%, P = 1.5e-13), had more atherogenic serum lipid profile (atherogenic index estimated as the TG/HDL cholesterol ratio 4.90, 0.72 – 25.6 vs. 3.79, 0.66 – 49.7, P = 0.003; HDL-cholesterol level 34.8, 17.3 – 103 vs. 40.0, 7 – 103 mg/dL, P = 0.0004; TG 167.0, 48.8 – 652 vs. 149.8, 40.0 – 856 mg/dL, P = 0.034), but similar RRT duration compared to deceased HD non-smokers. Cigarette smoking status did not influence cardiovascular mortality either in DM or non-DM group. DM smokers showed similar cardiovascular mortality to non-DM smokers, but among HD non-smokers, DM patients demonstrated higher cardiovascular mortality than non-DM subjects (P = 0.029). Among all smokers, the rs705379 TT genotype was associated with all cardiovascular (P = 0.028), all cardiac (P = 0.046), and cardiac non-related with CHD (P = 0.001) mortality. The rs705379 TT genotype smokers, who died from cardiac reasons, showed a higher frequency of myocardial infarction than CC+CT bearers (66.7% vs. 29.2%, P = 0.047). Non-DM smokers showed similar qualitative significance to all smokers concerning all cardiovascular, all cardiac, and cardiac non-related with CHD death rates (P-values 0.011, 0.044, and 0.009, respectively). In DM non-smokers, the rs705379 T allele correlated with CHD related deaths (P = 0.020). The rs854560 T allele, compared to the AA genotype, was associated with lower cardiovascular mortality in non-DM smokers (P = 0.008). The rs854560 TT genotype showed a negative correlation with cardiac death non-related to CHD in all non-smokers (P = 0.079). In DM smokers, the rs662 G allele was associated with a higher risk of cardiac mortality (P = 0.005). In all non-smokers and non-DM non-smokers, the rs662 G allele correlated with cardiovascular deaths (P = 0.020 and P = 0.018, respectively). Conclusion The variant alleles of PON1 rs705379 (T) and rs662 (G) are associated with cardiac mortality in HD patients. The rs854560 variant allele (T) possessors present better cardiovascular survival than the AA genotype subjects. Cardiovascular mortality is not merely related to polymorphic variants known as associated with lower serum activity or concentration of paraoxonase, a PON1 protein product. Assessing PON1 SNVs enables the prediction of cardiovascular mortality risk in HD smokers and non-smokers and may help select patients for advanced prevention against cardiovascular diseases.

İlk İnme Atağı Olan Olgularda Sessiz Serebral Lezyonların Trigliserid/HDL-Kolesterol Oranı ile İlişkisinin Değerlendirilmesi

Aim: Triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio is defined as the serum atherogenicity index. High TG/HDL-C ratio is related with vascular diseases, insulin resistance and metabolic syndrome. The TG/HDL-C ratio in cerebrovascular diseases, especially in silent cerebral lesions hasn’t been well studied. The aim of this study was to evaluate the frequency of silent cerebral ischemia (SCI) and leukoaraiosis (LA), and its relationship with TG/HDL-C ratio in patients admitted with the first ischemic stroke attack. Material and Methods: We retrospectively evaluated 200 patients who admitted to Bulent Ecevit University Faculty of Medicine, Department of Neurology with the diagnosis of acute first ischemic stroke. Silent cerebral lesions were defined as LA and SCI with magnetic resonance imaging. TG/HDL-C ratio was calculated by dividing TG levels by HDL-C levels. Results: Silent cerebral lesions were detected 124 (83.2%) of 149 patients. LA severity was evaluated according to Fazekas score, 22 (14.8%) of patients were grade 0, 49 (32.9%) of them were grade 1, and 78 (52.3%) of them were advanced periventricular white matter hyperintensity (adv-PWMH) group. TG/HDL-C ratio in SCI group was higher than the group without SCI, but it wasn’t statistically significant (p=0.091). A significant increase was observed in the TG/HDL-C ratio, as LA severity increased. TG/HDL-C ratio was significantly higher in adv-PWMH group (p=0.050). Conclusion: High serum atherogenicity index is associated with atherosclerosis and vascular endothelial dysfunction. With this simple, inexpensive and effective test method, high-risk group of LA and SCI could be identified.

Gender differences in serum atherogenicity and cardiovascular risk at older patients

Gender differences in serum atherogenicity and cardiovascular risk at older patients

Intracellular transports and atherogenesis.

There is a great progress in understanding the cellular and molecular aspects of atherosclerosis, which is one of the leading causes of death. Yet, there are questions regarding the cellular and metabolic mechanisms that lead to atherogenesis. Among the many factors that influence this process, food plays a significant role. Among other factors that play a paramount role in atherogensis are alterations of the transport of food in enterocytes, oxysterols, development of an atherogenic serum, endothelial damage, accumulation of foam cells within the vessel wall, lysosome-ER transport, and hypertension. Here, we discuss the contribution of secretion, transcytosis, endocytosis of chylomicrons, low-density lipoproteins (LDL), very LDL, and high-density lipoproteins to atherogenesis.

Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial.

ContextSaturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms.ObjectiveTo investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DesignDouble-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SettingGeneral community.ParticipantsMen and women who are overweight or have obesity (n = 61).InterventionMuffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet.Main Outcome MeasuresLean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.ResultsBy design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.ConclusionsSFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Assessing the impact of oral iodine supplementation on whole body iodine store, thyroid autoimmunity and serum biochemistry profile in women of childbearing age

Background and aimsIodine supplementation is advised for women with compromised iodine intake in the preconception period. The purpose of this study was to evaluate the benefits and harms of a supplementary dose of iodine (150 μg/day) for 90 days in women of childbearing age. Materials and methodsNon-pregnant females (n = 38; mean age: 24.1 ± 2.6 years; Range: 20–30) receiving a hall diet were enrolled. Measurements of urinary iodine excretion (UIC), thyroid autoimmunity biomarkers, serum clinical biochemistry profile and serum thyroglobulin were performed at baseline- and after iodine supplementation at 45- and 90 days, respectively. ResultsMedian UICs (μg/L) at baseline and after iodine intervention were 110, 304 and 310, respectively. This coincided with reductions in thyroglobulin, triacylglycerol, HDL-C, LDL-C, LDH, ALP and CPK levels as well as the prevalence of participants with UIC <150 μg/L. One new case of Tg-AB (+), a marked increase the titer of Tg-AB in one participant with TPO-AB (+)/Tg-AB (+) and two cases of increased thyroglobulin were observed after the iodine treatment. ConclusionsThis investigation indicates that in iodine sufficient regions, it might be difficult to maintain maternal iodine adequacy without iodine supplementation. The iodine supplementation was associated with improvement of atherogenic serum index, diminished levels of markers of cellular injury and a 42.1% drop in the prevalence of participants with maternal iodine deficiency. In instances, which screening of thyroid autoimmunity titers and thyroglobulin are not an option, we recommend the administration of iodine in lower dosages to prevent adverse and exaggerated autoimmune reactions.

THE ROLE OF GROUP EDUCATIONAL PROGRAMS IN MODIFICATION OF THE CARDIOVASCULAR RISK MAIN FACTORS

Aim – to study the influence of Healthy Schools "Healthy Lifestyle Basis" education on modifying of cardiovascular risk main factors. Materials and methods. 57 patients with cardiovascular diseases were examined. General clinical examination, anthropometric examinations (body weight, height, body mass index, and body composition), blood pressure measurement, and cholesterol determination, as well as its fractions in blood, were carried out before and after training course. The educational cycle included 9 lessons. Results. It was found that Healthy Schools education contributes to better both systolic and diastolic blood pressure monitoring. Thus, initially target blood pressure levels (&lt;140/90 mmHg for patients without diabetes mellitus and &lt;140/85 mmHg in case of diabetes) were observed in 49 % of patients, at the end of the training cycle – in 67 %. At the same time, the patients’ anthropometric parameters (BMI, fat and muscle tissue content, visceral fat) as well as cholesterol and its atherogenic serum fractions, did not change significantly. The patients’ education did not affect motivation level for their lifestyle improvement. So the number of patients consuming less than5 grams of table salt per day and over400 grams of vegetables and fruit did not change significantly. The level of physical activity between the examined patients did not change. Conclusion. The training course “Healthy Schools: Healthy Lifestyle Basis" contributes to improvement of blood pressure level monitoring, but does not significantly affect behavioral risk factors and does not lead to improvement of lipid metabolism monitoring in patients with cardiovascular disease. It is necessary to search for new more effective preventive care models for patients with high cardiovascular risk.

The cardiovascular risk factor profiles among end-stage renal failure patients treated with continuous ambulatory peritoneal dialysis and intermittent hemodialysis.

Cardiovascular (CV) event is the most common cause of death in dialysis patients. Both traditional and nontraditional CV risk factors related to malnutrition, inflammation, and anemia are commonly found in this population. This study was conducted to evaluate the burden factors of CV risk factors and its management in our regularly dialyzed patients. It was a single-center, cross-sectional analysis of prevalent intermittent hemodialysis (IHD) and continuous ambulatory peritoneal dialysis (CAPD) patients followed up in our hospital. Both the traditional and non-traditional CV risk factors were recorded and compared between the two groups. Eighty-eight patients were recruited. Forty-five were treated with CAPD and 43 patients were treated with IHD. The mean age was 49.5 ± 15.17 years old and 54.5% were females. Eighty percent were Malay followed by Chinese (14.7%) and Indian (5.7%). Thirty-eight percent were hypertensive and 17% were diabetic. The mean age of CAPD patients was 48.9 ± 16.9 compared to 50 ± 13.5 years old for IHD patients (P > 0.05). The body mass index (BMI) of CAPD patients was 23.9 kg/m2 versus 21.7 kg/m2 of the IHD (P = 0.04). The systolic and diastolic blood pressure of CAPD patients were 158 and 89 mm Hg in comparison to 141 and 72 mm Hg in IHD patients (P <0.001) and their total and low-density lipoprotein cholesterol level were 5.93 mmol/L and 3.84 mmol/L versus 4.79 mmol/L and 2.52 mmol/L, respectively (P≤0.001). The CAPD patients were hyperglycemic more than IHD patients, although it was not statistically significant. All the nontraditional CV risk factors except serum albumin were comparable between the two groups. Serum albumin in CAPD patients was 35.5 g/L compared to 40.8 g/L in the IHD patients (P <0.001). In our prevalent dialysis-dependent patients, both traditional and non-traditional CV risk factors are common. Due to the prolonged and continuous glucose exposure from the peritoneal dialysis fluid, the CAPD patients had highly atherogenic serum, higher BMI, and intensified inflammation which pre-disposed them to higher CV events.

Abstract 228: FADS2 Regulates Cardiometabolic Risk Phenotypes in Mice

Single nucleotide polymorphisms of the FADS2 gene associate with cardiometabolic risk in humans. Additionally, serum fatty acid profiles reflecting hepatic hyperactivity of the FADS2 gene product, delta-6 desaturase (D6D), correspond to cardiometabolic syndrome (CMS) phenotypes in humans and animal models. D6D catalyzes rate-limiting steps in essential polyunsaturated fatty acid (PUFA) metabolism, but its role in the pathogenesis of CMS has not been defined. In the present study, we employed pharmacological and genetic gain- and loss-of-function approaches to investigate the links between D6D activity and CMS phenotypes in mice. Transgenic overexpression (TG) of FADS2 in normal (FVB) mice modestly increases hepatic D6D protein expression and serum PUFA product/precursor ratios reflecting greater enzyme activity in vivo . FADS2 TG mice develop a mild, but progressive obesity and insulin resistance with age compared to WT mice, as well as elevated serum triglycerides and LDL/HDL and hepatic macrophage infiltration, but not hepatic steatosis. Global FADS2 ablation prevents obesity/insulin resistance and hyperlipidemia induced by high-fat feeding in C57Bl/6J mice, but promotes severe hepatic steatosis. Pharmacological D6D inhibition in vivo with SC-26196 (100 mpk 4-8 weeks) ameliorates hepatic inflammation and glucose intolerance in FADS2 TG mice and leptin-deficient ( ob ) mice, and prevents severe hyperlipidemia and atherosclerosis in ldlr -/- mice fed an atherogenic diet; despite augmenting hepatic steatosis in all cases. Tissue phospholipid analyses across these models revealed consistent positive relationships between D6D activity, pro-inflammatory eicosanoid accumulation, and a higher phosphatdiylcholine/phosphatidylethanolamine (PC/PE) ratio previously linked to increased hepatic VLDL synthesis and release. These studies establish an important role of D6D activity in the development of CMS and inflammation, and reveal novels links with tissue phospholipid class distribution and metabolism relevant to the development an atherogenic serum lipid profile, hepatic lipid homeostasis, and perhaps other aspects of cardiovascular risk currently under investigation in our laboratory.

Blood Serum Atherogenicity: Cellular Test for the Development of Anti- Atherosclerotic Therapy.

Atherosclerosis is one of the main problems in modern medical practice. This multifactorial disease can remain asymptomatic for a long time before manifesting itself in cardiovascular disorders, causing ischemic heart disease, myocardial infarction and even sudden death. Many synthetic drugs have been developed to reduce the symptoms of atherosclerosis, however, their efficacy in terms of reduction of atherosclerotic lesions progression is a matter of debate. Adverse effects of the exiting therapy should also be taken into account. The development of cellular models and improved understanding of the mechanisms of atherogenesis at the vascular wall level helped establishing the "direct anti-atherosclerosis therapy" approach. In this approach, the decrease of intracellular lipid deposition and atherogenicity of human blood serum are considered primary (direct) antiatherosclerotic effects. Screening of synthetic and natural substances for anti-atherosclerotic activity revealed a number of botanicals that could be used for direct anti-atherosclerotic therapy to treat early-stage atherosclerosis. As a result, 3 novel non-pharmaceutical products were developed (Allicor, Inflaminat and Karinat). Studies on in vitro and ex vivo models of atherogenesis confirmed their anti-atherosclerotic and anti-atherogenic activities and safety in patients. Clinical studies of Allicor, Inflminat and Karinat were carried out in subjects with diagnosed early stage atherosclerosis, demonstrating a clinically significant anti-atherosclerotic effect of the drugs. In this overview, we will present the complete process of the development of novel non-pharmaceutical products and report the results obtained in the conducted pre-clinical and clinical studies of these medications.

Prevalence and Predictors of Atherogenic Serum Lipoprotein Dyslipidemia in Women with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is associated with dyslipidemia. However, no study has focused on dyslipidemia in women with OSA. The aim of this study was to determine the prevalence and risk factors for dyslipidemia in women with OSA. Between 2007 and 2013, 570 eligible female patients with suspected OSA were consecutively recruited. The analyzed data consisted of polysomnography parameters, biochemical indicators, and anthropometric measurements. Serum lipid levels and dyslipidemia were compared. Binary logistic regression and multivariate linear regression models were used to determine the independent risk factors influencing serum lipids. After multivariate adjustment, there were essentially no major differences in serum lipid levels among patients with no to mild, moderate, and severe OSA nor did serum lipid levels change with OSA severity. Dyslipidemia in total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoproteins(apo) B and apoE increased with OSA severity, but only in non-obese subjects and those <55 years of age. Age, body mass index, waist to hip ratio, glucose and insulin were major risk factors for most serum lipids after multivariate adjustments. Our results indicate that, in women with OSA, age, obesity/central obesity, and insulin resistance are major determinants of dyslipidemia.