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The present study outlines the many risk variables of myocardial infarction (MI) in the patient population. Blood lipid profiles were normolipidemic in the study’s subjects. Myocardial infarction patients and controls were compared concerning their lipid, lipoprotein, and apolipoprotein profiles. Materials & methods: In this study, 84 participants had their blood cholesterol, Apolipoprotein-A, LDL, VLDL, HDL, triacylglycerols, and malondialdehyde studied. Out of the total number of participants, 42 were individuals who had suffered a myocardial infarction (MI). In contrast, the other 42 were controls matched for age and sex. Results: Acute myocardial infarction (MI) patients had significantly elevated levels of total cholesterol and triacylglycerols (TAGs) (p <0.05) despite the presence of low-density lipoprotein (LDL) in their blood. A significant difference was seen between the levels of apolipoprotein-A and low-density lipoprotein in the MI group and those in the control group. Researchers found that those who had a rapid heart attack exhibited significantly higher levels of malondialdehyde (p<0.05). Conclusion: For individuals diagnosed with risk factors, lipid profile monitoring, dietary antioxidant consumption, and measurement of inflammatory markers can all help lower the risk of myocardial infarction (MI). Furthermore, early detection can prevent MI. [ABSTRACT FROM AUTHOR]

For a healthy life, specialists recommend us to take care of what food we eat and to what extent we do it and how we approach a satisfying lifestyle. Cholesterol is not a bad thing, but often, in large quantities it becomes dangerous for human body. The medical world is faced with frequent changes in the concept of "normal values" of cholesterol, but also with a continuously developing pharmaceutical industry in this field, and the tendency is in this sense, towards an individualized treatment. This aspect in presented in our paper, which aims to describe the role of cholesterol in the functioning of human body; preventing the occurrence of heart diseases due increasing the level of cholesterol in the body and creating a healthy lifestyle that can reduce cholesterol levels. The paper presents some case studies on laboratory investigations of values cholesterol that includes determinations, studying and the research of medical equipment (Cobas Integra 400 Plus analyser), but also the results obtained during practice in the medical analysis laboratory.

Expression of LOX-1 and NOX1 genes in the human umbilical vein endotheliocytes (HUVECs) cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that among the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), the MDA-modified LDLs caused the greatest induction of the LOX-1 and NOX1 genes, as well as of the genes of antioxidant enzymes and genes of proapoptotic factors in HUVECs. Key role of the dicarbonyl-modified LDLs in the molecular mechanisms of vascular wall damage and endothelial dysfunction is discussed. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus with impaired transport of glucose from the blood into the cells against the background of absolute or relative hypoinsulinemia is accompanied by the development of dyslipidemia. Therefore, it is important to find therapeutic agents capable of alleviating the symptoms and, as a result, the course of diabetes. Screening of antidiabetic agents indicates that one of their main potential sources is natural products of plant origin. However, although a wide range of plant extracts are known to be used to treat diabetes, the use of only some of them has been scientifically proven. The aim of the study was to investigate the influence of biologically active substances available in the extracts of fruits of different cultivars of Cornus mas L. on plasma lipid profile in experimental diabetes mellitus. Materials and methods. Wistar male rats with starting weight of 140–170 g were used for all experiments. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg of body weight). The animals were divided into five groups. The first (control) and the second (diabetic control) groups orally received 1 mL of water daily for 14 days. Diabetic animals of the third to fifth groups were orally administered extracts of red and yellow fruits of Cornus mas L. and the “Loganic acid” extract, respectively, in the amount of 20 mg/kg of body weight for 14 days. The concentration of low-density lipoproteins, high-density lipoproteins, triglycerides, and cholesterol was determined in the rats’ blood plasma. Atherogenic indices were calculated based on lipid profile in blood plasma. Results. The total cholesterol content in diabetic rats’ blood plasma was reliably reduced when the extract of the red fruits of the Cornus mas L. “Podolski” cultivar was administered. “Loganic acid” extract, obtained from the yellow fruits of the “Yantarnyi” and “Flava” cultivars of Cornus mas L., decreased the concentration of total cholesterol, triglycerides, and the content of low-density lipoproteins against the background of an increase in the content of high-density lipoproteins in blood plasma. The atherogenic indexes made it possible to establish that the degree of risk of cardiovascular complications due to diabetes is significantly reduced against the background of the administration of extracts of cornelian cherry fruits. Conclusions. Extracts of the fruits of the “Podolski”, “Yantarnyi” and “Flava” cultivars of Cornus mas L. correct the lipid profile of blood plasma in streptozotocin-induced diabetes animals and, as a result, may potentially prevent the development of atherosclerotic changes and cardiovascular complications. The fruits of Cornus mas L. may be potential agents in the therapy of dyslipidemia in diabetes.

It has been established that acylhydroperoxy derivatives of phospholipids from oxidized rat liver mitochondria are captured predominantly by LDL particles but not by HDL during co-incubation with blood plasma lipoproteins, which refutes the previously suggested hypothesis about the involvement of HDL in the reverse transport of oxidized phospholipids and confirms the possibility of different mechanisms of lipohydroperoxide accumulation in LDL during oxidative stress. [ABSTRACT FROM AUTHOR]

This study evaluated the efficacy and safety of 20 mg of Cuban policosanol in blood pressure (BP) and lipid/lipoprotein parameters of healthy Japanese subjects via a placebo-controlled, randomized, and double-blinded human trial. After 12 weeks of consumption, the policosanol group showed significantly lower BP, glycated hemoglobin (HbA1c), and blood urea nitrogen (BUN) levels. The policosanol group also showed lower aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) levels at week 12 than those at week 0: A decrease of up to 9% (p < 0.05), 17% (p < 0.05), and 15% (p < 0.05) was observed, respectively. The policosanol group showed significantly higher HDL-C level and HDL-C/TC (%), approximately 9.5% (p < 0.001) and 7.2% (p = 0.003), respectively, than the placebo group and a difference in the point of time and group interaction (p < 0.001). In lipoprotein analysis, the policosanol group showed a decrease in oxidation and glycation extent in VLDL and LDL with an improvement of particle shape and morphology after 12 weeks. HDL from the policosanol group showed in vitro stronger antioxidant and in vivo anti-inflammatory abilities. In conclusion, 12 weeks of Cuban policosanolconsumption in Japanese subjects showed significant improvement in blood pressure, lipid profiles, hepatic functions, and HbA1c with enhancement of HDL functionalities. [ABSTRACT FROM AUTHOR]

Abstract Lipoproteins (LPs) are micelle‐like structures with a similar size to extracellular vesicles (EVs) and are therefore often co‐isolated, as intensively discussed within the EV community. LPs from human blood plasma are of particular interest as they are responsible for the deposition of cholesterol ester and other fats in the artery, causing lesions, and eventually atherosclerosis. Plasma lipoproteins can be divided according to their size, density and composition into chylomicrons (CM), very‐low‐density lipoproteins (VLDL), low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL). Here, we use atomic force microscopy for mechanical characterization of LPs. We show that the nanoindentation approach used for EV analysis can also be used to characterize LPs, revealing specific differences between some of the particles. Comparing LPs with each other, LDL exhibit a higher bending modulus as compared to CM and VLDL, which is likely related to differences in cholesterol and apolipoproteins. Furthermore, CM typically collapse on the surface after indentation and HDL exhibit a very low height after surface adhesion both being indications for the presence of LPs in an EV sample. Our analysis provides new systematic insights into the mechanical characteristics of LPs.

Keywords: free radical oxidation; antioxidants; low-density lipoproteins (LDL); oxidatively modified LDL; antioxidant enzymes; LOX-1; glycocalyx; endothelial dysfunction; vascular wall damage; atherosclerosis; diabetes EN free radical oxidation antioxidants low-density lipoproteins (LDL) oxidatively modified LDL antioxidant enzymes LOX-1 glycocalyx endothelial dysfunction vascular wall damage atherosclerosis diabetes N.PAG N.PAG 13 08/29/22 20220801 NES 220801 1. Based on the above data, we hypothesized a common molecular mechanism of vascular wall damage in atherosclerosis and diabetes mellitus, which includes an increase in chemical modification of apoB-100 LDL by dicarbonyls accumulated during free radical lipid peroxidation in atherosclerosis or autooxidation of glucose molecules in diabetes mellitus [[44]]. Indeed, it has been shown that "atherogenic" low-density lipoproteins (LDL) readily undergo oxidation both when incubated in the presence of vascular endotheliocytes and in the presence of free radical oxidation initiators [[12]]. When studying the atherogenicity (the efficiency of the capture of LDL particles by cultured human macrophages) of these two LDL modifications, we experimentally proved that not the "oxidized" (LOOH-containing LDL), but exclusively MDA-modified LDL bind to scavenger receptors of macrophages [[27]]. Thus, it should be recognized that the use of -TOH to inhibit LDL oxidizability in clinical trials is not justified and the use of coenzyme Q [[6], [100]] and other phenolic antioxidants, in particular probucol [[6], [101], [108], [110]], whose effectiveness in inhibiting LDL oxidation is convincingly confirmed, is more correctly for LDL protection against oxidation [[6], [101]]. [Extracted from the article]

The study aimed to assess the strength of the relationships between small dense low-density lipoproteins (sdLDL) and other parameters describing metabolic disorders and determine which of the lipid profile parameters can be used as markers of increased sdLDL concentration. The proposed model of sdLDL (examined by heparin–magnesium precipitation method) as a function of lipid parameters and atherogenic plasma indexes non-high-dense lipoproteins (non-HDL) and total cholesterol to high-dense lipoprotein ratio (TC/HDL), Atherogenic plasma index (API) is based on data from 485 participants divided into two age groups, <35≥ years. In multiple linear regression, sdLDL concentration was associated with the concentration of non-HDL-C (p = 0.043) and API value (p < 0.001) in participants <35 years, and with non-HDL-C (p < 0.001) and triglycerides (p = 0.020) concentration ≥35 years. The presence of abnormal values of API in participants <35 years and non-HDL-C in participants ≥35 years is a significant factor increasing the chances of the highest sdLDL (≥1.03 mmol/L) corresponding to Q4 in people without metabolic disorders. Different lipid parameters and atherogenicity indexes are associated with a high concentration of sdLDL depending on the age group. Abnormal API <35 years and non-HDL ≥35 years are associated with the highest sdLDL values and may be an indication for further specialist diagnosis of cardiovascular disease risk factors. [ABSTRACT FROM AUTHOR]

Atherosclerosis is one of the leading causes of death in developed and developing countries. The atherogenicity phenomenon cannot be separated from the role of modified low-density lipoproteins (LDL) in atherosclerosis development. Among the multiple modifications of LDL, desialylation deserves to be discussed separately, since its atherogenic effects and contribution to atherogenicity are often underestimated or, simply, forgotten. Vladimir Tertov is linked to the origin of the research related to desialylated lipoproteins, including the association of modified LDL with atherogenicity, autoimmune nature of atherosclerosis, and discovery of sialidase activity in blood plasma. The review will briefly discuss all the above-mentioned information, with a description of the current situation in the research. [ABSTRACT FROM AUTHOR]

The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one's lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer's disease and Parkinson's disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one's lifetime. [ABSTRACT FROM AUTHOR]

This paper addressed the prediction of heart sicknesses from hazard elements through a decision-making tree. We introduced the facts mining technique in public fitness to extract high-degree knowledge from raw data, which facilitates predicting heart diseases from risk factors and their prevention. The existing work intends to introduce a new risk element in heart diseases using novel data mining strategies. Latest actual international affected person's information (e.g., smoking, area of residence, age, weight, blood stress, chest pain, low-density lipoproteins (LDL), high-density lipoproteins (HDL), block arteries became accrued by way of the use of questionnaire through direct interview technique from patients. Novel two-variable decision trees are constructed for coronary heart illness records primarily based on chance factors and ranking of risk elements. The results show a correct prediction of cardiovascular disease (CVD) from the risk factor if records on chance factors are available as direct results of this study, tobacco, loss of physical exercise, and weight-reduction plan play a vital role in predicting heart diseases, which is the most important reason for mortality in developing countries, especially in my country. [ABSTRACT FROM AUTHOR]

The review presents evidence that the main damage to the vascular wall occurs not from the action of “oxidized” LDL, which contain hydroperoxy acyls in the phospholipids located in their outer layer, but from the action of LDL particles whose apoprotein B-100 is chemically modified with low molecular weight dicarbonyls, such as malondialdehyde, glyoxal, and methylglyoxal. It has been argued that dicarbonyl-modified LDL, which have the highest cholesterol content, are particularly “atherogenic”. High levels of dicarbonyl-modified LDL have been found to be characteristic of some mutations of apoprotein B-100. Based on the reviewed data, we hypothesized a common molecular mechanism underlying vascular wall damage in atherosclerosis and diabetes mellitus. The important role of oxidatively modified LDL in endothelial dysfunction is discussed in detail. In particular, the role of the interaction of the endothelial receptor LOX-1 with oxidatively modified LDL, which leads to the expression of NADPH oxidase, which in turn generates superoxide anion radical, is discussed. Such hyperproduction of ROS can cause destruction of the glycocalyx, a protective layer of endotheliocytes, and stimulation of apoptosis in these cells. On the whole, the accumulated evidence suggests that carbonyl modification of apoprotein B-100 of LDL is a key factor responsible for vascular wall damage leading to atherogenesis and endothelial dysfunction. Possible ways of pharmacological correction of free radical processes in atherogenesis and diabetogenesis are also discussed.

Atherosclerosis is one of the leading causes of death in developed and developing countries. The atherogenicity phenomenon cannot be separated from the role of modified low-density lipoproteins (LDL) in atherosclerosis development. Among the multiple modifications of LDL, desialylation deserves to be discussed separately, since its atherogenic effects and contribution to atherogenicity are often underestimated or, simply, forgotten. Vladimir Tertov is linked to the origin of the research related to desialylated lipoproteins, including the association of modified LDL with atherogenicity, autoimmune nature of atherosclerosis, and discovery of sialidase activity in blood plasma. The review will briefly discuss all the above-mentioned information, with a description of the current situation in the research.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is now considered an important contributor to the pathogenesis of atherosclerosis. The article describes the history of the discovery of PCSK9, the structure, functions and stages of biosynthesis of this molecule. PCSK9, through promoting lysosomal degradation of hepatic low-density lipoprotein receptor (LDLR), can decrease the clearance of plasma LDL, leading to hypercholesterolemia and formation atherosclerotic plaque formation. PCSK9 is a new therapeutic target for the treatment of hypercholesterolemia. New lipid-lowering drugs – PCSK9 inhibitors – are more effective than statins. Some studies have shown the involvement of PCSK9 in the inflammatory mechanisms of atherosclerosis.

Background: Preeclampsia represents one of the most frequent complications of pregnancy. There is physiological hyperlipidemia which leads to increase in serum levels of triglycerides and cholesterol in pregnancy. Abnormal lipid profile is associated with endothelial dysfunction. This study was conducted to evaluate the plasma level of lipids and its association with severity of preeclampsia. Materials and methods: A case-control study was conducted in 240 women with 120 women each in study and control group. Control group consisted of 120 normotensive pregnant women and study group consisted of 120 preeclamptic pregnant women. Serum lipid profile was estimated in both study and control group by fully automated ERBA xL-300 Biochemistry analyzer and statistical analysis was done by SPSS version 21.0. Results: In our study, maternal serum lipids were significantly deranged in pre-eclamptic group than compared to normal pregnant women and the results were significant. We also found that women with severe preeclampsia had highly deranged lipid profile as compared to women with mild preeclampsia. Conclusion: Preeclampsia is a common medical disorder of human pregnancy, complicating about 5-10% of all pregnancies. Deranged lipid profile levels are risk factor for endothelial dysfunction and vascular disease. [ABSTRACT FROM AUTHOR]

Hypercholestriolemia is major risk factor that enhances the incidence of cardiovascular disease and coronary artery disease. The present study was conducted to normalize the lipid profile in the blood by using Biocor Plus for hypercholesterolemia compared with Simvastatin. It was prospective randomized case control study conducted on 70 diagnosed patients of hypercholesterolemia at Sohail Memorial Hospital, Karachi and Amir Habib Medical Center and Maternity Home, Karachi. Patients of both genders (30-70 years) with clinical diagnosis of Hypercholesterolemia. Sample sizes for this study included total of 70 subjects. There was statistically significant difference when comparing the effectiveness of test drug, Biocor Plus to control drug, Simvastatin for the treatment of primary hypercholesterolemia. This is clearly evident that the herbal coded test drug, Biocor Plus possesses a therapeutic value for the treatment of primary hypercholesterolemia. There w ore no untoward or significant side effects associated with the use of Biocor Plus that proved its good acceptability by the patients. Moreover there was subjective feeling of wellbeing regarding breathlessness and chest tightness or pressure in the patients taking Biocor Plus. This makes an interesting point to focus on this effective alternative drug for primary hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Lipoproteins (LPs) are micelle-like structures with a similar size to extracellular vesicles (EVs) and are therefore often co-isolated, as intensively discussed within the EV community. LPs from human blood plasma are of particular interest as they are responsible for the deposition of cholesterol ester and other fats in the artery, causing lesions, and eventually atherosclerosis. Plasma lipoproteins can be divided according to their size, density and composition into chylomicrons (CM), very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Here, we use atomic force microscopy for mechanical characterization of LPs. We show that the nanoindentation approach used for EV analysis can also be used to characterize LPs, revealing specific differences between some of the particles. Comparing LPs with each other, LDL exhibit a higher bending modulus as compared to CM and VLDL, which is likely related to differences in cholesterol and apolipoproteins. Furthermore, CM typically collapse on the surface after indentation and HDL exhibit a very low height after surface adhesion both being indications for the presence of LPs in an EV sample. Our analysis provides new systematic insights into the mechanical characteristics of LPs., Competing Interests: The authors report no conflict of interest., (© 2022 The Authors. Journal of Extracellular Biology published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Highlights: [•] Antrodia salmonea exerts antioxidant activity against various oxidative systems. [•] Antrodia salmonea inhibited the AAPH-induced oxidative hemolysis in erythrocytes. [•] Antrodia salmonea inhibited the CuSO4-induced oxidative modification of human LDL. [•] The antioxidant potential of Antrodia salmonea is regarding their polyphenols. [ABSTRACT FROM AUTHOR]

Abstract: Background: The objective of this study is to investigate the association between childhood trauma and lipid profiles in adults from a highly traumatized population at-risk for cardiovascular disease. Method: We recruited 452 participants, primarily African-American and of low socioeconomic status, from general medical clinics in a large urban hospital. We performed direct comparisons, univariate analysis of variance and regression analyses together and separated by sex, examining the associations of child abuse, body mass index, lipid lowering drug use, blood pressure, age, and substance use to HDL levels and HDL/LDL ratios. Results: A history of moderate to severe levels of childhood trauma and abuse was associated with a significant decrease in HDL levels (P≤.01) and HDL/LDL ratios (P≤.001) relative to males with low levels of abuse. This relationship held when the status of lipid-lowering drugs was considered. When controlling for age, substance abuse, tobacco use, and adult trauma, the effects of childhood trauma remained significant. We found a significant child abuse by sex interaction on HDL/LDL ratios [F(1,369)=13.0, P≤.0005] consistent with a differential effect of trauma on dyslipidemia in male but not female subjects. Conclusions: Our data suggest that childhood trauma exposure, obtained with self-report measures, may contribute to increased risk of cardiovascular disease by way of stress-mediated alterations of lipid concentration and composition in male, but not female, subjects. [Copyright &y& Elsevier]

Abstract: The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. [Copyright &y& Elsevier]

Abstract: Patients with type 1 diabetes mellitus (T1DM) traditionally had a low body mass index and microangiopathic complications were common, while macroangiopathy and the metabolic syndrome were exceptional. The Diabetes Control and Complications Trial, published in 1993, demonstrated that therapy aimed at maintaining HbA1c levels as close to normal as feasible reduced the incidence of microangiopathy. Since then, the use of intensive insulin therapy to optimize metabolic control became generalized. Improved glycemic control resulted in a lower incidence of microangiopathy; however, its side effects included a higher rate of severe hypoglycemia and increased weight gain. Approximately 50% of patients with T1DM are currently obese or overweight, and between 8% and 40% meet the metabolic syndrome criteria. The components of the metabolic syndrome and insulin resistance have been linked to chronic T1DM complications, and cardiovascular disease is now the leading cause of death in these patients. Therefore, new therapeutic strategies are required in T1DM subjects, not only to intensively lower glycemia, but to control all associated metabolic syndrome traits. [Copyright &y& Elsevier]

Abstract: Mitochondria are essential sites for steroid hormone biosynthesis. Mitochondria in the steroidogenic cells of the adrenal, gonad, placenta and brain contain the cholesterol side-chain cleavage enzyme, P450scc, and its two electron-transfer partners, ferredoxin reductase and ferredoxin. This enzyme system converts cholesterol to pregnenolone and determines net steroidogenic capacity, so that it serves as the chronic regulator of steroidogenesis. Several other steroidogenic enzymes, including 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase and aldosterone synthase also reside in mitochondria. Similarly, the mitochondria of renal tubular cells contain two key enzymes participating in the activation and degradation of vitamin D. The access of cholesterol to the mitochondria is regulated by the steroidogenic acute regulatory protein, StAR, serving as the acute regulator of steroidogenesis. StAR action requires a complex multi-component molecular machine on the outer mitochondrial membrane (OMM). Components of this machine include the 18kDa translocator protein (TSPO), the voltage-dependent anion chanel (VDAC-1), TSPO-associated protein 7 (PAP7, ACBD3), and protein kinase A regulatory subunit 1α (PKAR1A). The precise fashion in which these proteins interact and move cholesterol from the OMM to P450scc, and the means by which cholesterol is loaded into the OMM, remain unclear. Human deficiency diseases have been described for StAR and for all the mitochondrial steroidogenic enzymes, but not for the electron transfer proteins or for the components of the cholesterol import machine. [Copyright &y& Elsevier]

Highlights: [•] Macrophages can internalise LDL through scavenger receptor-independent mechanisms. [•] Macropinocytosis has been shown to contribute significantly to foam cell formation. [•] Cytokines such as TGF-β, IL-33, IFN-γ and IL-17A can modulate macropinocytosis. [•] TGF-β mediated inhibition of macropinocytosis is a Smad-2/-3-independent process. [•] Macropinocytosis is a promising target for therapeutic intervention of atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies. Objective: The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high-fat diet (HFD). Methods: Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure (50 mg/kg ip ×4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression. Results: In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high-fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, coexposure reduced expression of hepatic genes implicated in β-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels. Conclusion: PCB 153 is an obesogen that exacerbates hepatic steatosis, alters adipocytokines and disrupts normal hepatic lipid metabolism when administered with HFD but not control diet. Because all US adults have been exposed to PCB 153, this particular nutrient–toxicant interaction potentially impacts human obesity/NAFLD. [Copyright &y& Elsevier]

Abstract: The incomplete inhibition of platelet function by acetylsalicylic acid (ASA), despite the patients are receiving therapeutic doses of the drug (‘aspirin-resistance’), is caused by numbers of risk factors. In this study we verified the idea that plasma homocysteine (Hcy) contributes to ‘aspirin-resistance’ in patients with coronary artery disease (CAD) and with or without type 2 diabetes mellitus (T2DM). A cross-designed randomized controlled intervention study has been performed (126 CAD pts incl. 26 with T2DM) to determine whether increasing ASA dose from 75mg to 150mg daily may result in the increased antiplatelet effect, in the course of four-week treatment. Platelet response to collagen (coll) or arachidonic acid (AA) was monitored with whole blood aggregometry, plasma thromboxane (Tx), and Hcy levels were determined immunochemically. The ASA-mediated reductions in platelet response to coll (by 12±3%) or AA (by 10±3%) and in plasma Tx (by 20±9%; p <0.02 or less) were significantly greater for higher ASA dose and significantly correlated with plasma Hcy, which was significantly lower in “good” ASA responders compared to “poor” responders (p <0.001). Higher plasma Hcy appeared a significant risk factor for blood platelet refractoriness to low ASA dose (OR=1.11; ±95%CI: 1.02–1.20, p <0.02, adjusted to age, sex and CAD risk factors). Hcy diminished in vitro antiplatelet effect of low ASA concentration and augmented platelet aggregation (by up to 62% (p <0.005) for coll and up to 15% (p <0.005) for AA), whereas its acetyl derivative acted oppositely. Otherwise, Hcy intensified antiplatelet action of high ASA. Hyperhomocysteinaemia may be a novel risk factor for the suppressed blood platelet response to ASA, and homocysteine may act as a specific sensitizer of blood platelets to some agonists. While homocysteine per se acts as a proaggregatory agent to blood platelets, its acetylated form is able to reverse this effect. Thus, these findings reveal a possibly new challenging potential of the acetylating properties of ASA therapy. [Copyright &y& Elsevier]

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m2. Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. [Copyright &y& Elsevier]

Abstract: Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucleotide polymorphisms (SNPs), R46L and E670G, in 5783 elderly participants in Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), of whom 43% had a history of vascular disease at baseline, and who were randomized to pravastatin or placebo with followup. In this population 3.5% were carriers of the T allele at R46L, and these subjects had significantly (p <0.001) lower levels of LDL C (mean, −10%), no difference in LDL C lowering response to pravastatin, and a non-significant 19% unadjusted and 9% adjusted decreased risk of vascular disease at baseline, with no on trial effect. Moreover, 6.0% were carriers of the G allele at E670G with no significant relationships with baseline LDL C, response to pravastatin, or vascular disease risk being observed. Our data support the concept that the rare allele of the R46L SNP at the PCSK9 locus significantly lowers LDL C, but does not greatly reduce CHD risk in an elderly population with a high prevalence of cardiovascular disease. [Copyright &y& Elsevier]

Abstract: Antioxidants from several nutrients, e.g. vitamin E, β-carotene, or flavonoids, inhibit the oxidative modification of low-density lipoproteins. This protective effect could possibly retard atherogenesis and in consequence avoid coronary heart diseases. Some studies have shown a positive effect of those antioxidants on cardiovascular disease. Another class of naturally occurring antioxidants are terpenoids, which are found in essential oils. The essential oil of Pinus mugo and the contained monoterpene terpinolene effectively prevent low-density lipoprotein (LDL)-oxidation. In order to test the mechanism by which terpinolene protects LDL from oxidation, LDL from human blood plasma enriched in terpinolene was isolated. In this preparation not only the lipid part of LDL is protected against copper-induced oxidation — as proven by following the formation of conjugated dienes, but also the oxidation of the protein part is inhibited, since loss of tryptophan fluorescence is strongly delayed. This inhibition is due to a retarded oxidation of intrinsic carotenoids of LDL, and not, as in the case of some flavonoids, attributable to a protection of intrinsic α-tocopherol. These results are in agreement with our previous results, which showed the same effects for a monoterpene from lemon oil, i.e. -terpinene. [Copyright &y& Elsevier]

Abstract: Purpose: To follow offspring of emigrants from Korea to China to assess the effects of obesity and urbanization/westernization on atherogenic risk profiles. Obesity and serum lipid levels during adolescence are associated with risk for atherosclerotic diseases during adulthood, but the effect of obesity on serum lipid levels in relatively lean populations is unclear, particularly among adolescents. Methods: The correlation of anthropometric measures with serum lipids was assessed in 2345 adolescents aged 16 to 18 years (four study groups: Korean-Chinese, n = 701; Korean-Rural, n = 671; Korean-Urban, n = 523; and Han-Chinese, n = 450). Results: Korean adolescents had higher average total cholesterol (TC) levels (146 mg/dl and 156 mg/dl for boys and girls, respectively) compared with Chinese adolescents (127 mg/dl and 143 mg/dl in China, respectively). The racial difference in atherogenic lipids (TC, low-density lipoprotein cholesterol [LDL-C], or their ratio to high-density lipoprotein cholesterol [HDL-C]) between Korean-Chinese and Han-Chinese was not found, but the urbanization difference among Korean adolescents (Korean-Chinese, Korean-Rural, and Korean-Urban) was obvious. The correlations of serum lipid levels with obesity indices were significant in TC, LDL-C, TC/HDL-C, LDL-C/HDL-C, and triglyceride (TG) among boys (p &#60; .001) and in HDL-C, TC/HDL-C, LDL-C/HDL-C, and TG among girls (p &#60; .05), but not strongly correlated (Pearson r &#60; .2). Conclusions: Significantly higher levels of TC and LDL-C (approximately 20 mg/dl) in Korean adolescents compared with Chinese adolescents were not owing to obesity or any racial difference. These findings underscore the importance of health promotion strategies including changes of lifestyle during childhood and adolescence. [Copyright &y& Elsevier]

Abstract: Therapies with antiretroviral protease inhibitors (ARPI) are correlated with a higher risk for dyslipidemia, hypercholesterolemia, and atherosclerosis. The original aim of this study was to establish whether α-tocopherol can reduce CD36 scavenger receptor overexpression occurring after treatment of monocytes with the ARPI ritonavir. We show here that treatment of THP-1 monocytes with ritonavir increases total protein and surface expression of CD36; however, only weak changes are observed at the mRNA level, suggesting that CD36 overexpression occurs mainly at the posttranscriptional level. Concentrations of ritonavir that upregulate CD36 expression inhibit proteasome activity in THP-1 cells, indicating a possible regulatory role of the proteasome in CD36 overexpression. Similar to ritonavir, the proteasome inhibitor ALLN increases the CD36 surface expression on THP-1 cells. α-Tocopherol efficiently normalizes CD36 protein overexpression after ritonavir treatment and reduces oxLDL uptake. Furthermore, in THP-1 monocytes, α-tocopherol reverses the proteasome activity inhibited by ritonavir. This study indicates that an increased CD36 protein expression in THP-1 monocytes induced by ritonavir can be normalized by α-tocopherol. CD36 overexpression is caused by inhibition of proteasome activity by ritonavir, which is efficiently restored by α-tocopherol. [Copyright &y& Elsevier]

Abstract: The association of paraoxonase-1 (PON1) with high-density lipoproteins (HDL) is a prerequisite for maintaining normal serum activity of the enzyme. The lipoprotein furnishes an amphipathic environment to shield the hydrophobic, N-terminal region of the enzyme, and such an environment may also be necessary for interaction of PON1 with its substrates. HDL provides the optimal physiological acceptor complex, in terms of both stimulating PON1 secretion and stabilizing the secreted peptide. Lipid and peptide components of HDL contribute to these effects, such that modulating HDL composition influences PON1 activity and function. In this context, understanding how PON1 associates with HDL, what governs the association, and the mechanism by which the PON1–HDL complex exerts its antioxidant function is of particular physiological relevance. Moreover, HDL is subject to substantial compositional variations under both normal and pathological metabolic conditions. It has implications for the influence of the enzyme on cardiovascular risk, as normal enzyme activity may not correlate with optimal functional (antioxidant) efficiency. We review evidence that HDL lipid and protein components interact to promote PON1 secretion and maintain serum enzyme activity. Emerging data on how the enzyme associates with HDL are discussed, and the consequences for PON1 function of modifications to HDL are outlined. Finally, we highlight questions concerning the HDL–PON1 association that remain unanswered but are of particular importance in defining PON1 efficiency. [Copyright &y& Elsevier]

We report that prosaposin binds to U937 and is active as a protective factor on tumor necrosis factor α (TNFα)-induced cell death. The prosaposin-derived saposin C binds to U937 cells in a concentration-dependent manner, suggesting that prosaposin behaves similarly. Prosaposin binding induces U937 cell death prevention, reducing both necrosis and apoptosis. This effect was inhibited by mitogen-activated protein ERK kinase (MEK) and sphingosine kinase (SK) inhibitors, indicating that prosaposin prevents cell apoptosis by activation of extracellular signal-regulated kinases (ERKs) and sphingosine kinase. Prosaposin led to rapid ERK phosphorylation in U937 cells as detected by anti-phospho-p44/42 mitogen-activated protein (MAP) kinase and anti-phosphotyrosine reactivity on ERK immunoprecipitates. It was partially prevented by apo B-100 and pertussis toxin (PT), suggesting that both lipoprotein receptor-related protein (LRP) receptor and Go-coupled receptor may play a role in the prosaposin-triggered pathway. Moreover, sphingosine kinase activity was increased by prosaposin treatment as demonstrated by the enhanced intracellular formation of sphingosine-1-phosphate (S-1-P). The observation that the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the prosaposin effect on cell apoptosis suggests that sphingosine kinase exerts its anti-apoptotic activity by the PI3K–Akt pathway.Thus, cell apoptosis prevention by prosaposin occurs through ERK phosphorylation and sphingosine kinase. The biological effect triggered by prosaposin might be extended to primary cells because it triggers Erk phosphorylation in peripheral blood mononuclear cells (PBMCs). This is the first evidence of a biological effect consequent to a signal transduction pathway triggered by prosaposin in cells of non-neurological origin. [Copyright &y& Elsevier]

Lectin-like oxidized LDL receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL in endothelial cells. In vitro, LOX-1 expression is induced by many inflammatory cytokines, oxidative stress, hemodynamic stimuli, and oxidized low-density lipoproteins (OxLDL). In vivo, the expression is enhanced in many proatherogenic settings including, hypertension, hyperlipidemia, and diabetes, and indeed accumulated in the atherosclerotic lesions. LOX-1 activation by OxLDL causes endothelial dysfunction/injury which is characterized by the generation of reactive oxygen species (ROS), subsequently inducing monocytes adhesion to endothelial cells, and endothelial apoptosis. Besides OxLDL, LOX-1 binds multiple classes of ligands including advanced glycation end products (AGE), activated platelets, and leukocytes, which may contribute to the pathogenesis of thrombosis and inflammation related to atherosclerosis. [Copyright &y& Elsevier]

Background: Coenzyme Q10 (CoQ10) originates from food intake as well as from endogenous synthesis. While plasma concentrations may be influenced by dietary uptake, little is known whether concentrations in plasma reflect or influence intracellular concentrations. Methods: For clinical routine investigation of intracellular CoQ10 contents, blood erythrocytes and platelets were isolated by Ficoll separating solution and CoQ10 analysed using HPLC. The intracellular concentrations were compared to environmental plasma concentrations of 50 clinically healthy infants and additionally after exogenous pharmaceutical supplementation of CoQ10 (3 mg/kg/day) to 12 adult probands for 14 days. Results: In healthy children, no correlation between plasma concentration and content in blood cells was found. A negative correlation exists between the year of life of the infants and CoQ10 concentrations in plasma correlated to cholesterol content. Probands supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 days. While excessive environmental supplementation was without influence on erythrocyte concentrations, a positive correlation exists between plasma content and concentrations in platelets as mitochondria containing cell lines. Conclusions: Under physiologically normal conditions, blood cells or organs may regulate their CoQ10 content independently from environmental supply. Effects may be expected in situations of deficiency or excessive supply. Erythrocyte concentration of CoQ10 keeps independent from environmental supply. Thus incorporation into outer cell membranes may be limited. However, an excessive environmental supply may influence inner compartments like mitochondrial membranes. [Copyright &y& Elsevier]

Apolipoprotein A-I (APOA-I) is the major protein component of high-density lipoproteins (HDL). It has been shown that over-expression of human APOA-I increases HDL cholesterol and decreases atherosclerosis. We constructed a helper-dependent adenoviral (HD-Ad) vector that contains the entire human APOA-I gene (hgAI). Intravenous delivery of 1×1013 viral particles/kg of this vector was followed by high levels of human APOA-I expression (up to 200 mg/dl) in the absence of detectable hepatic toxicity. We treated apo E-deficient mice with the hgAI vector and fed them either with a high-fat diet or with regular chow. As a control, two groups of mice were treated with PBS. The apo E-deficient mice treated with the hgAI vector showed supraphysiological levels of expression of human APOA-I at week 4 and high levels of HDL cholesterol compared to the control groups. Analysis of aortic atherosclerotic lesions 20 weeks after treatment, showed a significant reduction of lesion size in the treated mice with both diets. In conclusion, liver-directed gene transfer of human APOA-I using a HD-Ad vector resulted in a reduction of the development of atherosclerosis with the absence of significant toxicity. [Copyright &y& Elsevier]

The binding of photosensitizers to host molecules is discussed from the perspective of how the confinement in a molecular assembly influences the sensitizer’s photophysical properties. In connection with photodynamic therapy (PDT) of cancer during which the administered sensitizer necessarily interacts with the biological material the problem becomes of utmost importance. This review surveys changes of photophysical behaviour of porphyrins, metalloporphyrins and other porphyrinoid sensitizers induced by their interaction with biopolymers (proteins, nucleic acids), liposomes or synthetic sensitizer carriers (cyclodextrins, calixarenes). The structure, charge, and physicochemical properties of the sensitizer predetermine the type of interaction with the surrounding microenvironment and are manifested by changes in absorption, fluorescence, kinetics of deactivation of the excited states, and generation of singlet oxygen. As follows from the collected data, binding of the sensitizer does not restrict formation of the excited states but influences the kinetics. Various consequences of binding on the form and photophysical parameters of the sensitizers are discussed and general features of the mutual interaction are outlined. [Copyright &y& Elsevier]

Objectives: To explore the therapeutic potential of fibrates to attenuate premature atherosclerosis and cardiovascular disease in the atherogenic dyslipidemias typical of Type II diabetes, Metabolic Syndrome, and the Type IIB (mixed) lipid phenotype; such dyslipidemias frequently feature peripheral insulinoresistance. Background: Recent epidemiological data reveal that a marked increase in the prevalence of Type II diabetes, obesity and the Metabolic Syndrome has occurred on a worldwide scale. Dyslipidemia is an integral component of the metabolic perturbations which characterise these disorders, and is intimately associated with premature atherosclerosis and elevated cardiovascular risk. The atherogenic dyslipidemias of Type II diabetes, the Metabolic Syndrome and mixed (IIB) hyperlipidemia feature moderate to marked elevation of triglyceride-rich lipoproteins, low HDL-C cholesterol levels, and a dense LDL phenotype; equally, they feature an inflammatory state. Fibrates, agonists of PPARα, act to modulate the expression of key genes of lipid transport and metabolism in organs such as the liver and adipose tissue; equally, they exert pleiotropic, anti-inflammatory effects downregulating expression of genes encoding acute phase proteins and inflammatory cytokines. By inducing elevation of HDL-C levels, reduction in triglyceride-rich lipoproteins and a shift in the dense LDL phenotype to receptor-active, buoyant LDL, and by diminishing the inflammatory state, fibrates act to attenuate the atherosclerotic burden in atherogenic dyslipidemia. Such actions translate into significant clinical benefit as demonstrated by the reduction in cardiovascular morbi-mortality observed in both primary and secondary intervention trials (VA-HIT, Helsinki Heart Study, SENDCAP, DAIS, BECAIT). Conclusions: Fibrate therapy represents a cost effective approach to the clinical management of a wide spectrum of atherogenic dyslipidemias involving low HDL-C and elevated TGRL levels, and which include Type II diabetes and the Metabolic Syndrome. Optimised clinical application of these lipid modulating, anti-inflammatory drugs in these disorders in the context of either monotherapy or in combination with low dose statin is, therefore, warranted. [Copyright &y& Elsevier]

Cultured cells are able to oxidize low-density lipoproteins (LDL) and oxidized LDL (oxLDL), which are present in atherosclerosis areas, exhibit a variety of biological properties potentially involved in atherogenesis.This review is focused on the toxicity of oxLDL, more precisely on the toxic compounds generated during LDL oxidation, the features and the mechanisms of cell death (apoptosis or necrosis) induced by oxLDL. After internalization, toxic oxidized lipids, namely lipid peroxides, oxysterols and aldehydes, induce modifications of cell proteins, elicit oxidative stress, lipid peroxidation and alter various signaling pathways and gene expression. These events may participate in the toxic effect, and converge to trigger an intense, delayed and sustained calcium peak which elicits either apoptosis or necrosis processes. OxLDL-induced apoptosis involves both mitochondrial and death-receptor (Fas/FasL) apoptotic pathways, thereby activating the classical caspase cascade and subsequent biochemical and morphological apoptotic features. When apoptosis is blocked by overexpression of Bcl-2, oxLDL trigger necrosis through a calcium-dependent pathway.Apoptosis occurring in atherosclerotic areas is potentially involved in endothelial cell lining defects, necrotic core formation and plaque rupture or erosion which may trigger atherothrombotic events. However, the precise role of oxLDL in apoptosis/necrosis occurring in vivo in atherosclerotic plaques remains to be clarified. [Copyright &y& Elsevier]

Physiological parameters on hepatic and renal functionality and biodistribution, accumulation and elimination, in different organs of the 5,10,15,20-tetra (4-methoxyphenyl) porphyrin (TMP) were determined in Wistar rats. The transport of TMP by low-density (LDL) and high-density lipoproteins (HDL) was also investigated. The photosensitizer is accumulated in the spleen, where its concentration is significantly increased 21 d post-injection; it also accumulates in the liver and in a lower proportion, in the duodenum, and poorly in brain and muscle. The urine and serum biochemical parameters reached normal values both in control and treated groups. The glomerular filtrate rate was not affected by the TMP treatment in any of the studied times. These results would indicate that the sensitizer does not modify the renal glomerular function. TMP is mainly eliminated from the organism via the bile-gut pathway. Considering the total amount of porphyrin bound to both lipoproteins (LDL and HDL) in comparison with the total value of the TMP in serum, it can be inferred that a large amount of the agent is transported by lipoproteins in the plasma. This study proves information about the behavior of TMP in vivo under dark conditions. The results can be used to design photodynamic treatments using this porphyrin model as the sensitizer. [Copyright &y& Elsevier]

Background: Up-regulation of ICAM-1 at the vascular endothelial level is one of the most important promoters in the slow progression of a healthy vessel to an atherosclerotic one. The current study aimed to evaluate whether low dose of the antioxidant α-tocopherol affects the circulating soluble (s) ICAM-1 in healthy subjects. Methods: Either α-tocopherol E (50 I.U./day) or placebo was randomly, double-blindly given to 39 healthy male volunteers (mean age 41.6±5.9 years) over a period of 20 weeks. Results: At the baseline, sICAM-1 levels were inversely correlated with α-tocopherol concentrations (r=−0.525, p<0.0001). Twenty weeks of α-tocopherol supplementation (n=20 subjects) significantly decreased the circulating sICAM-1 levels (from 149.2±18.4 to 131.5±17.2 μg l−1, p<0.004) while it increased the α-tocopherol concentrations (from 25.8±5.0 to 31.2±5.7 μmol l−1, p<0.003). No significant changes in plasma sICAM-1 and α-tocopherol levels were observed in placebo-treated subjects (n=19). In actively treated subjects, changes in circulating sICAM-1 were inversely correlated with changes in α-tocopherol concentrations (r=−0.597, p=0.005). Conclusions: Plasma sICAM-1 concentrations are stable in healthy subjects over a period of 20 weeks while they significantly decreased with low dose of α-tocopherol. Thus, antioxidant vitamins are likely to counteract with endothelial changes that could potentially trigger the atherogenetic process. [Copyright &y& Elsevier]