Showing papers in "Current Opinion in Lipidology in 2002"

Dietary pattern analysis: a new direction in nutritional epidemiology.

Abstract: Recently, dietary pattern analysis has emerged as an alternative and complementary approach to examining the relationship between diet and the risk of chronic diseases. Instead of looking at individual nutrients or foods, pattern analysis examines the effects of overall diet. Conceptually, dietary patterns represent a broader picture of food and nutrient consumption, and may thus be more predictive of disease risk than individual foods or nutrients. Several studies have suggested that dietary patterns derived from factor or cluster analysis predict disease risk or mortality. In addition, there is growing interest in using dietary quality indices to evaluate whether adherence to a certain dietary pattern (e.g. Mediterranean pattern) or current dietary guidelines lowers the risk of disease. In this review, we describe the rationale for studying dietary patterns, and discuss quantitative methods for analysing dietary patterns and their reproducibility and validity, and the available evidence regarding the relationship between major dietary patterns and the risk of cardiovascular disease.

Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin

Abstract: Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation-stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin-induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation-stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation-stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation-stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin-resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator-activated receptor-gamma; an action may contribute to the insulin-sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.

Dietary polyunsaturated fatty acids and regulation of gene transcription.

Abstract: Dietary polyunsaturated fatty acids (PUFAs) are a source of energy and structural components for cells. PUFAs also have dramatic effects on gene expression by regulating the activity or abundance of four families of transcription factor, including peroxisome proliferator activated receptor (PPAR) (alpha, beta and gamma), liver X receptors (LXRs) (alpha and beta), hepatic nuclear factor-4 (HNF-4)alpha and sterol regulatory element binding proteins (SREBPs) 1 and 2. These transcription factors play a major role in hepatic carbohydrate, fatty acid, triglyceride, cholesterol and bile acid metabolism. Non-esterified fatty acids or fatty acid metabolites bind to and regulate the activity of PPARs, LXRs and HNF-4. In contrast, PUFAs regulate the nuclear abundance of SREBPs by controlling the proteolytic processing of SREBP precursors, or regulating transcription of the SREBP-1c gene or turnover of mRNA(SREBP-1c). The n3 and n6 PUFAs are feed-forward activators of PPARs, while these same fatty acids are feedback inhibitors of LXRs and SREBPs. Saturated fatty acyl coenzyme A thioesters activate HNF-4 alpha, while coenzyme A thioesters of PUFAs antagonize HNF-4 alpha action. Understanding how fatty acids regulate the activity and abundance of these and other transcription factors will likely provide insight into the development of novel therapeutic strategies for better management of whole body lipid and cholesterol metabolism.

Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health.

Abstract: Epidemiologic studies suggest an inverse association of tea consumption with cardiovascular disease The antioxidant effects of flavonoids in tea (including preventing oxidative damage to LDL) are among the potential mechanisms that could underlie the protective effects Other possible mechanisms include attenuating the inflammatory process in atherosclerosis, reducing thrombosis, promoting normal endothelial function, and blocking expression of cellular adhesion molecules Cocoa and chocolate can also be rich sources of flavonoids Flavanols and procyanidins isolated from cocoa exhibit strong antioxidant properties in-vitro In acute feeding studies, flavanol-rich cocoa and chocolate increased plasma antioxidant capacity and reduced platelet reactivity Based on limited data, approximately 150 mg of flavonoids is needed to trigger a rapid antioxidant effect and changes in prostacyclin Some dose-response evidence demonstrates an antioxidant effect with approximately 500 mg flavonoids Brewed tea typically contains approximately 172 mg total flavonoids per 235 ml (brewed for 2 min); hence, consumption of 1 and 35 cups of tea would be expected to elicit acute and chronic physiologic effects, respectively Chocolate is more variable with some products containing essentially no flavonoids (009 mg procyanidin/g), whereas others are high in flavonoids (4 mg procyanidin/g) Thus, approximate estimates of flavonoid rich chocolate needed to exert acute and chronic effects are 38 and 125 g, respectively Collectively, the antioxidant effects of flavonoid-rich foods may reduce cardiovascular disease risk

Lipoprotein lipase: the regulation of tissue specific expression and its role in lipid and energy metabolism

Abstract: Purpose of reviewThe aim of this review is to summarize and discuss recent advances in the understanding of the physiological role of lipoprotein lipase in lipid and energy metabolism.Recent findingsStudies on the transcriptional and the posttranscriptional level of lipoprotein lipase expression hav

Prebiotics and Lipid Metabolism

Abstract: Prebiotics are defined as nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth or the activity of one or a limited number of bacteria (bifidobacteria, lactobacilli) in the colon. Dietary fructans are nutritionally interesting oligosaccharides that strictly conform to the definition of prebiotics and (in view of experimental studies in animals and of less numerous studies in humans) exhibit interesting serum or hepatic lipid lowering properties. Other nondigestible/fermentable nutrients, which also modulate intestinal flora activity, exhibit cholesterol or triglyceride lowering effects. Are changes in intestinal bacterial flora composition or fermentation activity responsible for those effects? What is the future of prebiotics in the nutritional control of lipidaemia and cardiovascular disease risk in humans? Those questions only receive partial response in the present review because studies of the systemic effects of prebiotics are still in their infancy, and require fundamental research devoted to elucidating the biochemical and physiological events that allow prebiotics to exert systemic effects on lipid metabolism.

Cytochrome P450 pathways of arachidonic acid metabolism.

Abstract: Cytochrome P450s metabolize arachidonic acid to hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. These eicosanoids are formed in a tissue and cell-specific manner and have numerous biological functions. Of major interest are the opposing actions of hydroxyeicosatetraenoic and epoxyeicosatrienoic acids within the vasculature. Regio- and stereoisomeric epoxyeicosatrienoic acids have potent vasodilatory properties while 20-hydroxyeicosatetraenoic acid is a potent vasoconstrictor. Both effects are mediated through actions on large-conductance Ca2+-activated K+ channels. Cytochrome P450-derived eicosanoids are also important in the regulation of ion transport, and have recently been shown to influence a number of fundamental biological processes including cellular proliferation, apoptosis, inflammation, and hemostasis. The formation of these functionally relevant eicosanoids is tightly controlled by the expression and activity of the cytochrome P450 epoxygenases and hydroxylases. In addition, soluble epoxide hydrolase catalyzes the hydrolysis of epoxyeicosatrienoic acids to dihydroxyeicosatrienoic acids, and the activity of this enzyme is a critical determinant of tissue epoxyeicosatrienoic and dihydroxyeicosatrienoic acid levels. The intracellular balance between epoxyeicosatrienoic, dihydroxyeicosatrienoic and hydroxyeicosatetraenoic acids influences the biological response to these eicosanoids and alterations in their levels have recently been associated with certain pathological conditions. The involvement of the cytochrome P450-derived eicosanoids in a wide array of biological functions and the observation that levels are altered in pathological conditions suggest that the enzymes involved in the formation and degradation of these fatty acids may be novel therapeutic targets.

Arterial retention of apolipoprotein B48- and B100-containing lipoproteins in atherogenesis

Abstract: Purpose of reviewThe ‘response to retention’ hypothesis of atherosclerosissuggests that the arterial deposition of cholesterol is directlyproportional to the concentration of circulating plasmalipoproteins. However, there is increasing evidence to supportthe concept that specific lipoproteins may be preferentiallyretained within the arterial wall, possibly as a result of greateraffinity for cell surface and extracellular matrices.Recent findingsRecently, key studies have provided insight into mechanismsinvolved in the interaction of apolipoprotein B (apoB)-containinglipoproteins with extracellular matrices. In addition, novelmethods and innovative experimental design has enabled us todifferentiate between the delivery, retention and efflux ofapoB

Conjugated linoleic acid metabolism.

Abstract: Conjugated linoleic acid (CLA) is a naturally occurring fatty acid that is produced by a bio-hydrogenation process in the rumen, and thus is present in dairy products and ruminant meat. In this case the predominant isomer formed is 9cis,11trans. However, CLA includes 28 positional and geometrical isomers, of which only 9cis,11trans and 10trans,12cis have thus far been proven to possess biological activities. Both of these CLA isomers have been shown to undergo elongation and desaturation processes similar to those that occur with linoleic acid, maintaining the conjugated diene structure. There are evidences supporting the hypothesis that CLA metabolism may interfere with eicosanoid formation. Other metabolites with 16 carbon atoms (conjugated 16:2 and 16:3, which are probably derived from peroxisomal beta-oxidation of CLA and its metabolites, respectively) have been detected. This suggests an efficient metabolism of CLA and its metabolites in peroxisomes, which might be linked to their capacity to activate peroxisome proliferator-activated receptors.

Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis.

Abstract: Cytoplasmic fatty acid-binding proteins (FABPs) are a family of proteins, expressed in a tissue-specific manner, that bind fatty acid ligands and are involved in shuttling fatty acids to cellular compartments, modulating intracellular lipid metabolism, and regulating gene expression. Several members of the FABP family have been shown to have important roles in regulating metabolism and have links to the development of insulin resistance and the metabolic syndrome. Recent studies demonstrate a role for intestinal FABP in the control of dietary fatty acid absorption and chylomicron secretion. Heart FABP is essential for normal myocardial fatty acid oxidation and modulates fatty acid uptake in skeletal muscle. Liver FABP is directly involved in fatty acid ligand signaling to the nucleus and interacts with peroxisome proliferator-activated receptors in hepatocytes. The adipocyte FABP (aP2) has been shown to affect insulin sensitivity, lipid metabolism and lipolysis, and has recently been shown to play an important role in atherosclerosis. Interestingly, expression of aP2 by the macrophage promotes atherogenesis, thus providing a link between insulin resistance, intracellular fatty acid disposition, and foam cell formation. The FABPs are promising targets for the treatment of dyslipidemia, insulin resistance, and atherosclerosis in humans.

ATP-binding cassette transporter A1 and cholesterol trafficking.

Abstract: Purpose of reviewTwo hallmarks of cardiovascular disease are the presence of sterol-laden macrophages in the artery wall and reduced plasma HDL levels. A cell membrane protein named ATP-binding cassette transporter A1 (ABCA1) mediates secretion of excess cholesterol from cells into the HDL metabolic

Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells.

Abstract: There are several potential mechanisms by which HDLs protect against atherosclerosis. One relates to the ability of HDLs to promote the efflux of cholesterol from macrophages. Another is the ability of HDLs to inhibit one of the earliest events in the development of atherosclerosis, namely the expression of vascular cell adhesion molecules in activated endothelial cells. This property has been reported in vitro in studies with both native and reconstituted HDLs. The inhibitory activity of reconstituted HDLs is influenced by the phospholipid composition of the particles. An inhibition of endothelial cell adhesion molecule expression has also been observed in some (but not all) studies conducted in vivo in mice and pigs. The mechanism of this potentially anti-atherogenic effect of HDLs remains uncertain, as does its contribution to the cardioprotective effects of HDLs in vivo.

Lipid peroxidation in neurodegeneration: new insights into Alzheimer's disease.

Abstract: Imbalances of oxidative homeostasis and lipid peroxidation have been revealed as important factors involved in neurodegenerative disorders such as Alzheimer's disease. The brains of patients with Alzheimer's disease contain increased levels of lipid-peroxidation products such as 4-hydroxy-2-nonenal or acrolein, and enhanced lipid peroxidation can also be detected in cerebrospinal fluid and plasma from such patients. Recent research revealed that the interplay of transition metals, amyloid-beta peptide and lipid peroxidation might be responsible for increased oxidative stress and cell damage in this disease. In particular, the contrasting roles of amyloid-beta peptide, as a possible transition metal-chelating antioxidant for lipoproteins and a pro-oxidant when aggregated in brain tissue, has been the focus of discussion recently. In this context, lipid peroxidation has to be seen as an important part of the pathophysiological cascade in Alzheimer's disease, and its measurement in body fluids might serve as a therapy control for Alzheimer's disease and other neurodegenerative diseases.

Carbohydrate-induced hypertriglyceridemia: modifying factors and implications for cardiovascular risk.

Abstract: High-carbohydrate/low-fat, isocaloric diets have repeatedly been shown to increase plasma triglyceride concentrations. The present review addresses recent developments relevant to several important unresolved issues. These include the type of dietary carbohydrate that is most likely to induce hypertriglyceridemia, predictors of individual susceptibility, modifiable physiologic factors that may mitigate the plasma triglyceride response, underlying metabolic mechanisms that are responsible for increased plasma triglycerides, and implications of altered serum lipid profiles for atherogenic risk. Although some progress has been made in this field, the central public health issue - the net effect on cardiovascular risk - remains unresolved.

The paraoxonase gene family and coronary heart disease.

Abstract: Purpose of review The antioxidant activity of high-density lipoprotein is largely due to the paraoxonase 1 located on it. Experiments with transgenic paraoxonase 1 knock-out mice indicate the potential for this enzyme to protect against atherogenesis. This effect of high-density lipoprotein in decreasing low-density lipoprotein lipid peroxidation is maintained for longer than that of antioxidant vitamins and could thus be more protective. Several important advances in the field of paraoxonase research have occurred during this review period, not least the discovery that two other members of the paraoxonase gene family, PON2 and PON3, may also have important antioxidant properties. Significant advances have been made in understanding the basic biochemical function of paraoxonase 1 and the discovery of possible modulators of its activity. Recent findings Decreased coronary heart disease risk associated with polymorphisms of paraoxonase 1, which are most active in lipid peroxide hydrolysis, as revealed by meta-analysis is likely to be an underestimate of the true contribution of paraoxonase 1 to coronary heart disease because these polymorphisms explain only a small component of the variation in paraoxonase 1 activity. It is a very important observation, however, because genetic influences are not likely to be confounded by other factors linked with both coronary heart disease and diminished paraoxonase 1 activity. Summary Although advances have been made in research into the paraoxonase family and atherosclerosis, much more needs to be done. Paraoxonase 1 is much the most extensively researched and strategies will hopefully emerge to increase its activity and provide a more satisfactory test of the antioxidant hypothesis of atherosclerosis than antioxidant vitamins have done.

Phospholipid transfer protein.

Abstract: A role for phospholipid transfer protein (PLTP) in HDL remodelling and in the formation of pre-beta-HDL is now well established, both in vivo and in vitro. Over-expression of human PLTP in C57BL6 mice lowers plasma HDL levels, probably because of increased HDL catabolism. Despite these low HDL levels, plasma from these mice mitigates cholesterol accumulation in macrophages and has increased potential for pre-beta-HDL formation. Plasma HDL concentration is also decreased in PLTP knockout mice. These intriguing observations can be explained by recent studies that indicate that PLTP is not only involved in remodelling of HDL subfractions but also in VLDL turnover. The role of PLTP in atherogenesis and VLDL synthesis was demonstrated in transgenic mouse models with increased susceptibility for the development of atherosclerosis, bred into PLTP knockout mice. The data clearly show that PLTP can be proatherogenic. As mentioned above, however, PLTP may have antiatherogenic potential in wild-type C57BL6 mice. Information regarding the role and regulation of PLTP in human (patho)physiology is still relatively sparse but accumulating rapidly. PLTP activity is elevated in diabetes mellitus (both type 1 and type 2), obesity and insulin resistance.

Oxidized fat in the diet, postprandial lipaemia and cardiovascular disease.

Abstract: Accumulating evidence suggests that oxidized fats and lipid oxidation products in the diet can contribute to the pathogenesis of atherosclerosis. The present review summarizes studies that show that oxidized fat and lipid oxidation products are present in human foods; that these compounds are absorbed by the intestine and appear in the blood circulation; and that these ingested substances can have deleterious cardiovascular effects in both humans and experimental animals. However, considerable additional research is required to establish the extent to which dietary fat oxidation poses a threat to human health and/or longevity.

Cd14 signalling in lipid rafts: new ligands and co-receptors

Abstract: Purpose of review Lipid rafts on monocytes/macrophages provide a dynamic microenvironment for an integrated lipopolysaccharide receptor (CD14)-dependent clustering of a set of receptors involved in innate immunity and clearance of atherogenic lipoproteins. The purpose of this review is to summarize the recent advances in our understanding of CD14-dependent receptor clustering and its relevance in atherogenesis. Recent findings Upon binding of various ligands, CD14 as a multiligand pattern recognition receptor induces specific coassembly of additional receptors present on circulating monocytes. Summary The composition of the receptor cluster and thus the associated signalling pathways defines a ligand specific cellular response, linking endogenous and exogenous host defense to a common recognition platform in rafts.

Inflammatory markers and coronary heart disease.

Abstract: Purpose of review Despite changes in lifestyle and the use of effective pharmacologic interventions to lower cholesterol levels, coronary heart disease remains the major cause of morbidity and mortality in the developed world. Cholesterol screening fails to identify almost 50% of those individuals who will present with acute coronary syndromes. Recent evidence from laboratory and prospective clinical studies demonstrates that atherosclerosis is not simply a disease of lipid deposition, but rather is an inflammatory process with highly specific cellular and molecular responses. The clinical utility of inflammatory markers has been examined in a variety of atherothrombotic diseases. Because C-reactive protein is highly stable in stored frozen samples, and automated and robust analytical systems for its measurement are available, it has become the most widely examined inflammatory marker. Recent findings C-reactive protein has consistently been shown to be a useful prognostic indicator in acute coronary syndromes and is a strong predictor of future coronary events in apparently healthy individuals. In addition, C-reactive protein can identify individuals with normal lipid levels who are at increased risk for future coronary events. Because drugs such as aspirin and statins reduce inflammatory risk, C-reactive protein has the potential to guide the use of these therapies in high-risk individuals for primary prevention. Summary C-reactive protein may have a role in global risk assessment for primary prevention and in targeting those patients who will benefit from anti-inflammatory therapies. In addition, it may also be a good prognostic indicator in patients with acute coronary syndromes.

Oxidized lipids as mediators of coronary heart disease.

Abstract: Purpose of review To summarize the recent evidence on the physiological relevance of the view that LDL lipid oxidation may play a major role in the inflammatory reaction that leads to or amplifies atherogenesis. Oxidation of LDL phospholipids containing arachidonic acid at the sn-2 position occurs when a critical concentration of ‘seeding molecules’ derived from the lipoxygenase pathway is reached in LDL. This generates a series of biologically active, oxidized phospholipids that mediate the cellular events seen in the developing fatty streak. Recent findings We have observed that LDL from mice that are genetically predisposed to diet-induced atherosclerosis is highly proinflammatory when the mice are maintained on an atherogenic diet, when they are injected with LDL-derived oxidized phospholipids, or once they are infected with influenza A virus. Patients with coronary atherosclerosis also had highly proinflammatory LDL, despite having normal blood lipid levels or normal plasma HDL levels. Summary We and others have hypothesized that HDL and LDL-derived oxidized phospholipids may be part of a system of nonspecific innate immunity. We therefore propose that determination of HDL capacity against LDL oxidation and the detection of proinflammatory HDL may be a useful marker of susceptibility to atherosclerosis.

Sequestration of aggregated low-density lipoproteins by macrophages

Abstract: Purpose of review Evidence suggests that much of the LDL in atherosclerotic plaques is aggregated. Aggregation of LDL could be an important factor that determines how this lipoprotein is metabolized by plaque macrophages and the fate of aggregated LDL cholesterol within plaques. This review discusses a novel endocytic pathway by which macrophages process aggregated LDL. Recent findings Recently, it has been shown that aggregated LDL can be sequestered in macrophage surface-connected compartments and plasma membrane invaginations by a process termed patocytosis. In contrast to rapid degradation of LDL and aggregated LDL taken up by macrophages through pinocytosis and phagocytosis, respectively, aggregated LDL sequestered in macrophages undergoes only limited degradation. Macrophages can disaggregate and release sequestered aggregated LDL by activating plasminogen to plasmin. Plasmin degrades LDL apolipoprotein B sufficiently to disaggregate the aggregated LDL, releasing it from the macrophage surface-connected compartments. In contrast, activating macrophages with phorbol-myristate-acetate stimulates degradation of aggregated LDL and inhibits plasminogen-mediated release of the aggregated lipoprotein from macrophage surface-connected compartments. Summary Macrophage sequestration of aggregated LDL is a unique endocytic pathway relevant not only to the processing of aggregated LDL in atherosclerotic plaques but also for the processing of other materials, such as hydrophobic particles that trigger this endocytic pathway. Macrophage sequestration of aggregated LDL can result in different fates for the aggregated LDL, depending on the state of macrophage activation and the functioning of the plasminogen-based fibrinolytic system. Patocytosis of aggregated LDL should be considered in addition to phagocytosis as a possible uptake pathway in studies of macrophage processing of aggregated LDL.

The myotoxicity of statins.

Abstract: Purpose of reviewSince hypercholesterolaemia is a chronic condition, the long-term safety of statins is important. Adverse reactions involving skeletal muscle are the most common (reported incidence 1-7%). The recent withdrawal of cerivastatin because of deaths from rhabdomyolysis, of which 25% were

Phenotypic variability in familial hypercholesterolaemia: an update.

Abstract: Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia. The present review discusses recent developments in this field.

Safety considerations for statins

Abstract: Purpose of reviewThe hydroxymethyl glutaryl coenzyme A reductase inhibitors or statins offer important benefits for the large populations of individuals at high risk for coronary heart disease. These drugs have a good safety profile. Nevertheless, differences in physicochemical and pharmacokinetic p

Recent discoveries in inclusive food-based approaches and dietary patterns for reduction in risk for cardiovascular disease.

Abstract: Purpose of review To discuss new evidence-based dietary recommendations founded on an inclusive food strategy and to address the challenges that are posed by integrating a growing list of heart healthy foods into the diet without increasing energy intake beyond that required to achieve a healthy body weight. Recent findings New food-based dietary recommendations issued by the American Heart Association with the objective of reducing risk for cardiovascular disease (CVD) promote an inclusionary approach. The American Heart Association recommends a variety of foods to target four major goals: achieve a healthy overall diet, achieve a healthy weight, promote desirable lipid levels, and promote desirable blood pressure. Specific foods recommended include fruits and vegetables, grain products (including whole grains), fish, lean meat and poultry, fat-free or low-fat dairy products, and legumes. In addition, the new National Cholesterol Education Program Adult Treatment Panel III recommends reductions in saturated fat and cholesterol and therapeutic dietary options for enhancing LDL-cholesterol lowering, with inclusion of plant stanols/sterols (2 g/day) and increased viscous (soluble) fiber (10-25 g/day). In parallel with the evolution of new dietary recommendations is the expanding list of specific foods that have cardioprotective effects. Additional foods on this list are nuts, soy, legumes, alcohol, tea, and garlic. Summary It will be challenging to include all foods that reduce CVD risk in the diet and still maintain energy control. Strategies are needed that facilitate developing heart healthy dietary patterns that maximally reduce CVD risk.

Oxysterols in human circulation: which role do they have?

Abstract: Oxysterols are oxygenated derivatives of cholesterol that are intermediates in cholesterol excretion pathways. They may also be regarded as transport forms of cholesterol and introduction of an additional hydroxyl group facilitates flux of cholesterol across cell membranes and the blood-brain barrie

Recent studies on interactions between n-3 and n-6 polyunsaturated fatty acids in brain and other tissues.

Abstract: Recent literature provides a basis for understanding the behavioral, functional, and structural consequences of nutritional deprivation or disease-related abnormalities of n-3 polyunsaturated fatty acids. The literature suggests that these effects are mediated through competition between n-3 and n-6 polyunsaturated fatty acids at certain enzymatic steps, particularly those involving polyunsaturated fatty acid elongation and desaturation. One critical enzymatic site is a delta6-desaturase. On the other hand, an in-vivo method in rats, applied following chronic n-3 nutritional deprivation or chronic administration of lithium, indicates that the cycles of de-esterification/re-esterification of docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) within brain phospholipids operate independently of each other, and thus that the enzymes regulating each of these cycles are not likely sites of n-3/n-6 competition.

The APOE locus and the pharmacogenetics of lipid response.

Abstract: Genetic variation at the APOE locus has been associated with plasma lipoprotein concentrations in the fasting (low-density, and high-density lipoproteins and triglycerides), and in the postprandial (triglyceride-rich lipoproteins) states. Resulting from these associations, the APOE locus has been found to be a significant genetic determinant of cardiovascular disease in the general population. Beyond the traditional association studies, APOE genetic variation has been shown to play a significant role, which explains some of the individual variations in therapies aimed at normalizing plasma lipid concentrations. Thus, the APOE E4 allele has been shown in some studies to be associated with increased response to dietary intervention. Conversely, APOE E2 carriers appear to be more responsive to statin therapy. The mechanisms behind these observations, however, have not been elucidated. Moreover, several other gene : environment and gene : therapy interactions have recently been demonstrated, thus further increasing the interest in this remarkable apolipoprotein.

Regulation of endothelial cell apoptosis in atherothrombosis

Abstract: Increasing evidence suggests that endothelial cell apoptosis might contribute to atherogenesis, plaque erosion and acute coronary syndromes. The present review article summarizes the current findings and discusses the potential role of endothelial cell apoptosis for coronary artery disease progression. Moreover, the signalling events that critically regulate endothelial cell apoptosis are discussed. The article focuses on the regulation of endothelial cell apoptosis by the redox balance, which is mainly determined by reactive oxygen species and nitric oxide. Moreover, the role of S-nitrosylation of protein targets for protection of endothelial cell apoptosis will be discussed.

New factors in the regulation of adipose differentiation and metabolism.

Abstract: Obesity and lipoatrophy are major risks for insulin resistance, type 2 diabetes and cardiovascular diseases. The molecular links between adipocyte dysfunction and metabolic disorders were elusive until the discovery that adipose tissue operates as an endocrine organ and releases factors targeting a wide range of organs. This article attempts to review the more recent advances from research on the transcriptional control of adipogenesis and on new adipocyte-secreted proteins that have been proposed as molecular links between adipose tissue and insulin resistance.