Accumulation Of Remnant Lipoproteins Research Articles

Evaluation of remnant lipoprotein accumulation by measuring non-HDL-cholesterol minus direct LDL cholesterol level (non-HDL-C-dLDL-C) instead of measuring remnant cholesterol levels

Evaluation of remnant lipoprotein accumulation by measuring non-HDL-cholesterol minus direct LDL cholesterol level (non-HDL-C-dLDL-C) instead of measuring remnant cholesterol levels

Palmar Striated Xanthomas in Clinical Practice.

Context Palmar striated xanthomas (PSX) are macular subcutaneous lesions conferring a yellow-to-orange coloration of palmar and finger creases that characterize dysbetalipoproteinemia, a disease associated with sustained plasma accumulation of triglyceride-rich lipoprotein remnants. Although remnants accumulation may occur in any condition interfering with triglyceride-rich lipoprotein hydrolysis or clearance, the presence of PSX has not been systematically assessed across the spectrum of lipid disorders potentially associated with sustained or recurrent remnants accumulation.ObjectiveThe aim of this study was to assess the occurrence of (PSX) in a wide spectrum of lipid disorders ranging from very severe hypercholesterolemia (homozygous familial hypercholesterolemia) to very severe hypertriglyceridemia (chylomicronemia).MethodsThis study involved 3382 dyslipidemic White adult patients (1856 men and 1526 women) seen at the Chicoutimi Hospital Lipid Clinic (Quebec, Canada), covering a wide range of lipid disorders, from severe hypertriglyceridemia to severe hypercholesterolemia. Categorical variables were compared using the Pearson χ 2 statistic, whereas univariate analysis of variance or nonparametric Kruskal-Wallis was used for continuous variables.ResultsA total of 5.1% (173/3382) of the studied patients presented PSX, a majority of them (67.1%) being women. PSX were observed in 18.8% of patients with dysbetalipoproteinemia and also among 14.1% of hypertriglyceridemic patients with partial lipoprotein lipase deficiency, 3.7% of patients with chylomicronemia, and in all those with homozygous familial hypercholesterolemia. Overall, 10.7% of patients with PSX did not meet dysbetalipoproteinemia diagnosis criteria.ConclusionAccording to our study, the PSX prevalence estimate among patients without dysbetalipoproteinemia would be around 10% and they could be observed in a wide spectrum of lipid disorders associated with recurrent or sustained remnant lipoprotein accumulation.

29-LB: Investigating the Molecular Basis of the Microbiota-Mediated Regulation of Postprandial Chylomicron Production

Obesity and insulin resistance have been identified as major global health concerns. They are associated with increased intestinal chylomicron production and subsequent remnant lipoprotein accumulation which lead to postprandial dyslipidemia. Dietary composition influences metabolic output of the gut microbiota by digesting dietary nutrients and producing various metabolites, which affects host metabolism. Understanding the mechanistic roles of the microbiota in regulating host lipid metabolism is therefore critical in addressing the pathogenesis of dyslipidemia. In this study, we aimed to investigate the effects of microbiota on lipid and lipoprotein metabolism in Syrian golden hamsters which is a more relevant animal model to human. Microbiota depletion was induced in male and female hamsters given either standard chow or a low fat/high fructose (HF) diet via antibiotic oral gavage administration. The results showed that feeding a HF diet increased plasma triglyceride (TG) and cholesterol (CH) levels while substantially reduced microbiota in antibiotic-administered groups led to significant reduction in circulating TG and CH in both diets. Then, we intended to look at the role of dysbiosis on postprandial lipid accumulation. Interestingly, in both sexes postprandial and TRL-TG levels were dramatically reduced after antibiotic administration; the effect was associated with significantly decreased ApoB48 protein levels. These changes appear to be due to a modulation of genes involved in farnesoid X receptor (FXR) receptor signaling in the ileum. Additionally, some critical genes implicated in lipid synthesis and absorption were also altered in the jejunum, with the most remarkable discovery being the extremely substantial down regulation of Scavenger Receptor Class B type 1“SR-B1” at both the mRNA and protein levels in all antibiotic-treated groups independent of sex and diet. In summary, our results suggest a novel role for the gut microbiota in regulating lipid and lipoprotein metabolism in the gut, urging further studies to determine the underlying mechanisms. Disclosure N. H. S. Abdalqadir: None. K. Adeli: None. Funding Canadian Institutes of Health Research

Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts

Background and aimsFamilial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE ε2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit – notably adiposity or insulin resistance – is required, but the association between these risk factors and development of FD has not been studied prospectively. MethodsFor this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE ε2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia – likely to be FD – was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated. ResultsEleven of the 69 ε2ε2 subjects (16%) developed dyslipidemia – likely FD – during follow-up. Age-, sex- and cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04–1.39), waist circumference (OR 1.26 95%CI 1.01–1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04–18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia. ConclusionsAdiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE ε2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD.

Risk factors for the presence and development of Familial Dysbetalipoproteinemia in subjects from the general population with an APOE2E2 genotype

Abstract Background Subjects who carry one or two ɛ2 alleles of the APOE gene are protected from cardiovascular disease due to low LDL-cholesterol levels. However, 10–18% of ɛ2 homozygotes (ɛ2ɛ2) develop Familial Dysbetalipoproteinemia (FD), which is characterized by extensive remnant lipoprotein accumulation, making it a good model to study the effect of remnants on atherosclerosis and cardiovascular disease. Important causal factors for FD, or an “FD like phenotype” in ɛ2 heterozygotes (ɛ2ɛ3), are thought to be adiposity and insulin resistance. However, to date this relation was only evaluated in cross-sectional studies. Purpose To evaluate the cross-sectional and longitudinal association of adiposity and insulin resistance on the presence and development of FD in ɛ2ɛ2 or an “FD-like” phenotype in ɛ2ɛ3 subjects. Methods For this study we included 18042 subjects with an APOE measurement from two Dutch population-based cohorts; the PREVEND cohort (follow-up 4.1 (interquartile range (IQR) 4.0–4.4) years) and the Rotterdam Study (follow-up 10.1 (IQR 5.6–10.8) years). Subjects with an ɛ3ɛ3 genotype (n=10391) and ɛ4 carriers were excluded (n=5265). FD and “FD like” phenotype were defined as triglyceride levels >3 mmol/l or use of lipid lowering medication. Logistic regression models were used to evaluate the effect of age, sex, BMI, waist circumference, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) on FD lipid phenotype. Changes in adiposity measures and insulin resistance between baseline and follow-up were compared in subjects with and without development of FD at follow-up. Results In total, 2386 subjects were included of whom 118 participants had ɛ2ɛ2 and 2268 had ɛ2ɛ3 of whom 68% completed a follow-up visit. Subjects mean age was 59±14 years and 44% were male. In ɛ2ɛ2 subjects, 19% (n=23) had FD at baseline and 16% (n=11) developed FD during follow-up. In ɛ2ɛ3 subjects 13% (n=305) had an “FD like” phenotype at baseline and 11% (n=146) at follow-up. Cross-sectional determinants for the presence of an FD or “FD like” phenotype at baseline were male sex, BMI, waist circumference and non-lipid MetS criteria. In ɛ2ɛ2 subjects who developed FD during follow-up, markers of adiposity and insulin resistance did not change compared to baseline. However, these FD patients more often had adiposity (BMI, weight and waist circumference) and T2DM at baseline, compared to those and who did not developed FD. Conclusions These results show for the first time that adiposity and insulin resistance are important risk markers for future development of FD or “FD like” phenotype in ɛ2ɛ2- and ɛ2ɛ3 subjects. The increased susceptibility of ɛ2 carriers for development of an FD lipid phenotype by adiposity and insulin resistance might be due to impaired remnant clearance consequent to decreased binding affinity of APOɛ2 to the LDL-receptor in combination with degradation of the heparan sulfate receptor by insulin resistance (mediated by sulfatase 2 activation). Odds Ratios for FD lipid phenotype Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): UMC Utrecht; Erasmus MC; UMC Groningen

A simplified diagnosis algorithm for dysbetalipoproteinemia

Dysbetalipoproteinemia (DBL) is a disease of remnant lipoprotein accumulation caused by a defective apolipoprotein (apo) E and is associated with a considerable atherogenic burden. However, there exists confusion concerning the diagnosis of this disorder, and as a consequence, misdiagnosis is frequent. The objective of the present study is to propose an algorithm for the diagnosis of DBL using simple clinical variables. In a large cohort of 12,434 dyslipidemic patients, 4891 patients presented with mixed dyslipidemia (total cholesterol≥5.2mmol/L [200mg/dL] and triglycerides≥2.0mmol/L [175mg/dL]), and 188 DBL patients were identified based on the presence of an elevated very-low-density lipoprotein cholesterol/triglyceride ratio and were carriers of apoE2/E2. The APOE genotype or phenotype as well as the lipoprotein ultracentrifugation results were available for all patients. Among the laboratory variables associated with the lipid profile, the non-high-density lipoprotein cholesterol (HDL-C)/apoB ratio was the best predictor of DBL diagnosis based on the C-statistic. Previous proposed criteria had either low sensitivity or low specificity for the diagnosis of DBL. Using a non-HDL-C/apoB cut point of 3.69mmol/g (1.43 in conventional units) followed by the presence of apoE2/E2 resulted in a good sensitivity (94.8%), negative predictive value (99.8%), specificity (99.6%), positive predictive value (88.5%), accuracy (99.4%), and area under the curve (0.97 [0.95-0.99]) for the prediction of DBL. We therefore propose a 3-step algorithm for the diagnosis of DBL using total cholesterol and triglycerides as a first step, the non-HDL-C/apoB ratio as a second screening criterion and finally the APOE genotype, lipoprotein ultracentrifugation, or electrophoresis as a confirmatory test.

New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease.

Over the past few decades, atherogenic dyslipidaemia has become one of the most common phenotypic presentations of lipid abnormalities, being strongly and unequivocally associated with an increased risk of cardiovascular (CV) disease. Despite the excellent results achieved from statin and non-statin management of LDL cholesterol and CV events prevention, there still remains a significant residual risk, associated with the prevalence of non-LDL cholesterol lipid patterns characterised by elevated triglyceride levels, low HDL cholesterol, a preponderance of small and dense LDL particles, accumulation of remnant lipoproteins and postprandial hyperlipidaemia. These qualitative and quantitative lipid modifications are largely associated with insulin resistance, type 2 diabetes and obesity, the prevalence of which has grown to epidemic proportions throughout the world. In this review, we analyse the pathophysiology of this particular dyslipidaemia, its relationship with the development of atherosclerotic CV disease and, finally, briefly describe the therapeutic approaches, including changes in lifestyle and current pharmacological interventions to manage these lipid alterations aimed at preventing CV events.

Postprandial dyslipidemia in insulin resistant states in adolescent populations.

Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults, but also in adolescents. The metabolic syndrome, a complex cluster of metabolic abnormalities, increases one's risk of developing type 2 diabetes and cardiovascular disease (CVD). Dyslipidemia, a key component of the metabolic syndrome, is highly associated with insulin resistance and contributes to increased CVD risk. Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e. fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)]. However, the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk. In insulin resistant states, the intestine overproduces triglyceride-rich lipoprotein (TRL) particles, termed chylomicrons (CMs), following ingestion of a fat-containing meal, as well as in the fasting state. Along with elevated hepatic TRLs (i.e. very-low density lipoproteins), CMs contribute to remnant lipoprotein accumulation, small dense LDL particles, and reduced HDL-C, which collectively increase CVD risk. Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence, studying postprandial dyslipidemia in the adolescent population is an important area of study. Postprandial dyslipidemia in the pediatric population poses a significant public health concern, warranting a better understanding of its pathogenesis and association with insulin resistance and CVD. This review discusses the metabolic syndrome, focusing on the link between insulin resistance, postprandial dyslipidemia, and CVD risk. Furthermore, the clinical significance and functional assessment of postprandial dyslipidemia, specifically in the adolescent population, is discussed in more detail.

Effects of a Dipeptidyl Peptidase 4 Inhibitor Sitagliptin on Glycemic Control and Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus (GLORIA Trial).

Aim: The morbidity of cardiovascular disease in patients with type 2 diabetes mellitus (DM) deteriorates in combination with dyslipidemia. The accumulation of remnant lipoproteins in patients with fasting and postprandial hypertriglyceridemia is highly atherogenic. The current study investigated whether the dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates dyslipidemia and hyperglycemia.Methods: We enrolled 38 patients with type 2 DM (20 males and 18 females, 65.7 ± 9.9 years old, HbA1c levels < 8.4%), and all patients gave written informed consent. Sitagliptin (50 mg/day) was added to current antidiabetic treatments and increased to 100 mg/day to achieve low HbA1c levels (< 7.4%). Glucose and lipoprotein metabolism profiles were analyzed at 0, 4, and 12 weeks after sitagliptin administration.Results: Sitagliptin significantly decreased fasting levels of triglyceride (TG) (161 ± 90 vs. 130 ± 66 mg/dl, p < 0.01) and non-HDL-C (129 ± 29 vs. 116 ± 20 mg/dl, p < 0.01) in combination with glucose (150 ± 47 vs. 129 ± 27 mg/dl, p < 0.01) and HbA1c (7.1 ± 0.6 vs. 6.6 ± 0.7 mg/dl, p < 0.001). Sitagliptin also significantly decreased the fasting levels of apolipoprotein (apo) B-48 (7.8 ± 6.7 vs. 5.6 ± 4.0 µg/ml, p < 0.01), remnant lipoprotein cholesterol (15.3 ± 9.5 vs. 12.0 ± 7.9 mg/dl, p < 0.05) and other apolipoproteins, such as apoB, apoC-II, apoC-III, and apoE. Analyses of the lipoprotein profiles of fasting sera revealed that sitagliptin significantly decreased cholesterol and TG levels of lipoprotein fractions in the size of very low density lipoprotein and low density lipoprotein.Conclusions: These findings indicated that sitagliptin administration ameliorated the lipid and lipoprotein profiles in patients with diabetes, which may be due to the decrease in atherogenic remnant lipoproteins (UMIN#000013218).Abbreviations: apoapolipoproteinASCVDatherosclerotic cardiovascular diseaseCHDcoronary heart diseaseCLEIAchemiluminescence enzyme immunoassayCMChylomicronDPP-4dipeptidyl peptidase-4FFAsfree fatty acidsHPLChigh-performance liquid chromatographyIMTintima-media thicknessLDLlow-density lipoproteinLPLlipoprotein lipasePHTGpostprandial hypertriglyceridemiaRemL-Cremnant lipoprotein cholesterolRLP-Cremnant-like particle cholesterolTGtriglycerideTRLtriglyceride-rich lipoproteinVLDLvery low density lipoprotein

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.

Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events.

Dysbetalipoproteinemia: an extreme disorder of remnant metabolism.

Lipoprotein metabolism and the role of apolipoprotein E in the pathogenesis of dysbetalipoproteinemia. Remnant lipoproteins, modulated by lifestyle and genetic factors, are atherogenic. Dysbetalipoproteinemia could be viewed as a monogenic disorder of remnant metabolism. Elevated plasma triglyceride and cholesterol concentrations (mixed hyperlipidemias) are commonly encountered and dysbetaliproteinemia should be considered in this setting. Dysbetalipoproteinemia (remnant clearance disease, Fredrickson type III hyperlipidemia) is an uncommon dyslipoproteinemia related to mutations in apolipoprotein E that disrupt the clearance of remnants of triglyceride-rich lipoproteins; it may be overlooked because xanthomata of the skin and/or tendons occur in a minority of patients. The diagnosis ideally requires the demonstration of remnant lipoprotein accumulation and a genetic cause. Genotyping for apolipoprotein E2 may not prove the diagnosis as it may be associated with low plasma lipid values. The recent association of remnant lipoproteins with atherosclerosis along with many factors that modulate remnant lipoprotein metabolism underscores the importance of recognising dysbetalipoproteinemia as an extreme state of remnant lipoprotein accumulation. Although there may be some differences between remnants in the general population and dysbetalipoproteinemia, it is clear that remnants promote atherosclerosis. Current treatment strategies are adequate but new strategies could also be of benefit in dysbetalipoproteinemia.

Gerald M. Reaven, MD: Demonstration of the central role of insulin resistance in type 2 diabetes and cardiovascular disease.

Gerald M. Reaven, MD, could easily be epitomized as the “Father of Insulin Resistance.” (For those who do not know Dr. Reaven, he would humbly raise objection to being called Dr. Reaven rather than Jerry.) That said, Jerry is credited with developing the insulin suppression test, the first quantitative method to measure insulin-mediated glucose uptake in humans (1). Using this technique, he established the importance of insulin resistance in human disease, and importantly, in type 2 diabetes (2,3). In nondiabetic individuals, he demonstrated the role of insulin resistance/compensatory hyperinsulinemia in the development of 1 ) hypertriglyceridemia (4) and low HDL concentrations (5), 2 ) decreased urinary uric acid clearance and hyperuricemia (6), 3 ) decreased LDL particle diameter (7), 4 ) enhanced postprandial lipemia and remnant lipoprotein accumulation (8), 5 ) increased levels of plasminogen activator inhibitor-1 (9), 6 ) salt sensitivity (10), 7 ) essential hypertension (11), and 8 ) increased sympathetic nervous system activity (12). In addition to emphasizing the role of insulin resistance/compensatory hyperinsulinemia in increasing the likelihood of an individual developing one or more of the consequences listed above, he first pointed out the clustering of these abnormalities. It is clear now that this group of clinical abnormalities, initially designated Syndrome X, is an important factor leading to cardiovascular disease. Syndrome X was introduced to the medical community in his now famous Banting Lecture in 1988 (13) and only later became known as metabolic syndrome. Jerry was born in Gary, IN, on 28 July 1928, but spent most of his precollege years living in Cleveland, OH, thus accounting for his lifelong allegiance to the Cleveland Indians baseball team and a great deal of frustration on his part during their many less-than-stellar seasons. Jerry matriculated at the University of Chicago and graduated in 1949, also the year of his marriage to his …

Kidney Function, Cholesterol Absorption and Remnant Lipoprotein Accumulation in Patients with Diabetes Mellitus

Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) μg/mL and 2.3 (1.7-3.0) μg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.

Hepatic lipase activity is decreased in Japanese patients with type III hyperlipoproteinemia

BackgroundType III hyperlipoproteinemia (HLP), a disorder associated with a high incidence of premature cardiovascular diseases, is characterized by the accumulation of remnant lipoproteins in the plasma. The primary genetic defect in patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been thought to be attributable to the presence of apoE2, which bind poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance. On the other hand, the activity of hepatic lipase (HL), the enzyme that plays a pivotal role in the removal of remnant lipoproteins, in type III HLP has not been investigated. MethodsWe examined post-heparin plasma lipoprotein lipase (LPL) and HL activities in 7 patients with type III HLP. The activities of HL and LPL in post-heparin plasma were measured separately by an immunochemical method using antiserum specifically directed against HL. ResultsThe post-heparin plasma HL activity was significantly reduced, while the LPL activity was normal. ConclusionsReduced HL activity may account, at least in part, for the accumulation of remnant lipoproteins in the plasma, a characteristic feature of type III HLP.

Understanding Postprandial Inflammation and Its Relationship to Lifestyle Behaviour and Metabolic Diseases

Postprandial hyperlipidemia with accumulation of remnant lipoproteins is a common metabolic disturbance associated with atherosclerosis and vascular dysfunction, particularly during chronic disease states such as obesity, the metabolic syndrome and, diabetes. Remnant lipoproteins become attached to the vascular wall, where they can penetrate intact endothelium causing foam cell formation. Postprandial remnant lipoproteins can activate circulating leukocytes, upregulate the expression of endothelial adhesion molecules, facilitate adhesion and migration of inflammatory cells into the subendothelial space, and activate the complement system. Since humans are postprandial most of the day, the continuous generation of remnants after each meal may be one of the triggers for the development of atherosclerosis. Modulation of postprandial lipemia by lifestyle changes and pharmacological interventions could result in a further decrease of cardiovascular mortality and morbidity. This paper will provide an update on current concepts concerning the relationship between postprandial lipemia, inflammation, vascular function, and therapeutic options.

Disappearance of Angina Pectoris by Lipid-Lowering in Type III Hyperlipoproteinemia

Type III hyperlipoproteinemia is a rare familial disease characterized by marked elevations of serum cholesterol and triglyceride levels caused by an accumulation of remnant lipoproteins in apolipoprotein E2/E2 homozygotes. It is associated with an increased risk for premature atherosclerotic vascular disease. A 55-year-old woman was diagnosed as having type III hyperlipoproteinemia on the basis of skin lesions, serum lipid levels, lipid electrophoresis, and apolipoprotein E genotyping and stable angina pectoris on the basis of typical symptoms and treadmill exercise electrocardiographic results. After 1 year of combination therapy with atorvastatin and fenofibrate, skin xanthomata disappeared, leaving minimal remnants. In addition, there was no exertional chest pain, and treadmill exercise electrocardiographic results were negative. This finding was confirmed by coronary computed tomographic angiography. This case suggests that proper medical therapy can induce the regression of uncomplicated coronary lesions in type III hyperlipoproteinemia.

MS407 REDUCED MYOCARDIAL GLUCOSE UTILIZATION AFTER FASTING AND HEPARIN INJECTION IN RATS

Type III hyperlipoproteinemia (HLP), a disorder associated with a high incidence of premature cardiovascular diseases, is characterized by the accumulation of remnant lipoproteins in the plasma. The primary genetic defect in patients with type III HLP is the presence of apolipoprotein E2 (apoE2), an isoform of apoE, and accumulation of remnant lipoproteins in the plasma has been thought to be attributable to the presence of apoE2, which bind poorly to low density lipoprotein receptors, resulting in defective remnant lipoprotein clearance. On the other hand, the activity of hepatic lipase (HL), the enzyme that plays a pivotal role in the removal of remnant lipoproteins, in type III HLP has not been investigated.We examined post-heparin plasma lipoprotein lipase (LPL) and HL activities in 7 patients with type III HLP. The activities of HL and LPL in post-heparin plasma were measured separately by an immunochemical method using antiserum specifically directed against HL.The post-heparin plasma HL activity was significantly reduced, while the LPL activity was normal.Reduced HL activity may account, at least in part, for the accumulation of remnant lipoproteins in the plasma, a characteristic feature of type III HLP.

Unraveling hyperlipidemia type III (dysbetalipoproteinemia), slowly

The expression of type III hyperlipidemia (HLP) is the topic of the paper by Peter Henneman and his colleagues.1 Only very few lipid disorders seem to be more complex and poorly understood than the type III HLP by Fredrickson (or so-called dysbetalipoproteinemia). This is true despite the fact that type III HLP had been described in great detail more than 33 years ago2 and since then had been studied intensively by the most dedicated, leading lipid researchers worldwide. Type III HLP is a genetic disorder characterized by the accumulation of remnant lipoproteins in the plasma and development of premature atherosclerosis.

Increased lipoprotein remnant cholesterol levels in HIV-positive patients during antiretroviral therapy

Increased levels of postprandial triglycerides (TG) and remnant like particles (RLP) are associated with cardiovascular disease. We evaluated whether postprandial lipemia differed in HIV-positive patients with or without different antiretroviral regimens. A standardized high fat load was administered to 28 subjects: 11 HIV-positive subjects receiving protease inhibitors (PI), 10 HIV-positive subjects receiving non-nucleoside reverse transcriptase inhibitors (NNRTI) and 7 HIV-positive subjects not receiving highly active antiretroviral therapy, HAART (Naïve). Baseline TG levels and TG area under the curve (AUC) did not differ among the three groups. The postprandial TG concentration curves were similar in the NNRTI and Naïve groups, peaking at 3–5-h. Baseline RLP cholesterol was higher in the NNRTI group compared to other two groups ( P = 0.035). Both HAART groups (NNRTI and PI) had higher postprandial RLP cholesterol AUC than the Naïve group ( P = 0.024, ANOVA). In conclusion, during HIV conditions, HAART resulted in a pro-atherogenic pattern with accumulation of remnant lipoproteins.

Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation

The triacylglycerol content of chylomicrons and VLDL (very-low-density lipoprotein) compete for the same lipolytic pathway in the capillary beds. Although chylomicron triacylglycerols appear to be the favoured substrate for lipoprotein lipase, VLDL particles compete in numbers. Methods to quantify the specific triacylglycerol removal from VLDL and chylomicrons may involve endogenous labelling of the triacylglycerol substrate with stable isotopes in combination with arteriovenous blood sampling in humans. Arteriovenous quantification of remnant lipoproteins suggests that adipose tissue with its high lipoprotein lipase activity is a principal site for generation of remnant lipoproteins. Under circumstances of reduced efficiency in the removal of triacylglycerols from lipoproteins, there is accumulation of remnant lipoproteins, which are potentially atherogenic.