RESUMO
Dyslipidemia and inflammation exacerbate postprandial metabolic stress in people with diabetes. Acute dietary supplementation with polyphenols shows promise in improving postprandial metabolic stress in type 2 diabetes (T2D). Cocoa is a rich source of dietary polyphenols with demonstrated cardioprotective effects in adults without diabetes. To date, the acute effects of cocoa on postprandial lipids and inflammation have received little attention in the presence of T2D. This report expands on our earlier observation that polyphenol-rich cocoa, given as a beverage with a fast-food-style, high-fat breakfast, increased postprandial high-density lipoprotein-cholesterol (HDL-C) in adults with T2D. We now test whether polyphenol-rich cocoa modulated postprandial apolipoproteins (Apo-A1, B), non-esterified fatty acids, nuclear magnetic resonance (NMR)-derived lipoprotein subclass profiles, and select biomarkers of inflammation following the same dietary challenge. We found that cocoa decreased NMR-derived concentrations of total very low-density lipoprotein and chylomicron particles and increased the concentration of total HDL particles over the 6-hour postprandial phase. Serum interleukin-18 was decreased by cocoa vs. placebo. Thus, polyphenol-rich cocoa may alleviate postprandial dyslipidemia and inflammation following a high-fat dietary challenge in adults with T2D. The study was registered at clinicaltrials.gov as NCT01886989.
Assuntos
Chocolate , Diabetes Mellitus Tipo 2/metabolismo , Gorduras na Dieta , Lipoproteínas , Período Pós-Prandial/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Método Duplo-Cego , Feminino , Humanos , Inflamação/metabolismo , Lipoproteínas/sangue , Lipoproteínas/classificação , Lipoproteínas/metabolismo , Masculino , Pessoa de Meia-Idade , Preparações de Plantas/farmacologiaRESUMO
Soy protein and fish oil are food components that decrease the risk of cardiovascular disease. Previous studies demonstrated that these food components reduced serum cholesterol levels and suppressed hepatic lipogenesis. However, the underlying mechanisms of action of these food components remain unclear. Ten classes of serum lipoprotein profiles showed that dietary tofu, a soybean curd, suppressed cholesterol absorption, while fish oil reduced most of the lipoprotein classes in rats. Tofu and fish oil both halved the level of the lipoprotein class LAC1 (LDL-anti-protease complex), a 15-nm LDL-anti-protease complex, which is speculated to be a cause of atherosclerosis. Moreover, a global transcriptome analysis revealed that tofu inhibited the mRNA expression of genes involved in hepatic lipogenesis, while fish oil stimulated that of genes related to fatty acid degradation. Therefore, tofu and fish oil independently regulate lipid metabolism. The decrease observed in LAC1 may have been due to reduced cholesterol absorption in the tofu diet group and the interference of lipogenesis via the activation of polyunsaturated fatty acid detoxification in the fish oil group.
Assuntos
Óleos de Peixe/administração & dosagem , Lipídeos/sangue , Lipoproteínas/sangue , Alimentos de Soja , Adsorção , Animais , Colesterol/sangue , Colesterol na Dieta/farmacocinética , Ácidos Graxos/metabolismo , Ontologia Genética , Metabolismo dos Lipídeos , Lipogênese/genética , Lipoproteínas/química , Lipoproteínas/classificação , Fígado/metabolismo , Masculino , Modelos Biológicos , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transcriptoma , Triglicerídeos/sangueRESUMO
AIMS: There is limited knowledge about the association of lipoprotein particles and markers of coronary atherosclerosis such as coronary artery calcification (CAC) in relatively young high-risk persons. This study examines the association of lipoprotein subfractions and CAC in high cardiometabolic risk individuals. METHODS: The study presents analysis from baseline data of a randomized trial targeted at high-risk workers. Employees of Baptist Health South Florida with metabolic syndrome or diabetes were recruited. At baseline, all 182 participants had lipoprotein subfraction analysis using the ion mobility technique and participants above 35 years (N=170) had CAC test done. Principal components (PC) were computed for the combination of lipoprotein subclasses. Multiple bootstrapped regression analyses (BSA) were conducted to assess the relationship between lipoprotein subfractions and CAC. RESULTS: The study population (N=170) was largely female (84%) with a mean age of 58 years. Three PCs accounted for 88% variation in the sample. PC2, with main contributions from VLDL particles in the positive direction and large LDL particles in the negative direction was associated with a 22% increase in CAC odds (P value ï¼0.05 in 100% of BSA). PC3, with main contributions from HDL lipoprotein particles in the positive direction and small/medium LDL and large IDL particles in the negative direction, was associated with a 9% reduction in CAC odds (Pï¼0.05 in 88% of BSA). PC1, which had approximately even contributions from HDL, LDL, IDL and VLDL lipoprotein subfractions in the positive direction, was not associated with CAC. CONCLUSION: In a relatively young but high-risk population, a lipoprotein profile predominated by triglyceride-rich lipoproteins was associated with increased risk of CAC, while one predominated by HDL lipoproteins offered modest protection. Lipoprotein sub-fraction analysis may help to further discriminate patients who require more intensive cardiovascular work-up and treatment.
Assuntos
Biomarcadores/sangue , Calcinose/sangue , Doença da Artéria Coronariana/sangue , Espectrometria de Mobilidade Iônica/métodos , Lipoproteínas/sangue , Lipoproteínas/classificação , Calcinose/complicações , Calcinose/patologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/metabolismo , Animais , Biomarcadores , Doenças Cardiovasculares/etiologia , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas/classificação , Lipoproteínas/metabolismo , Lipoproteínas HDL/sangue , Oxirredução/efeitos dos fármacosRESUMO
A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European-Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African-Americans (AAs), 1450 Hispanic-Americans (HAs), and 775 Chinese-Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study center, and genetic ancestry (based on principal components), and additionally adjusted for Mexican/Non-Mexican status in HAs. A false discovery rate correction was applied separately within the results for each ethnicity to correct for multiple testing. Power calculations revealed that we did not have the power for SNP-based measures of association, so we analyzed phenotype-specific genetic risk scores (GRSs), constructed as in the original genome-wide analysis. We successfully replicated all 15 GRS-lipoprotein associations in 2527 EAs. Among the 15 significant GRS-lipoprotein associations in EAs, 11 were significant in AAs, 13 in HAs, and 1 in CHNs. Further analyses revealed that ethnicity differences could not be explained by differences in linkage disequilibrium, lipid lowering drugs, diabetes, or gender. Our study emphasizes the importance of ethnicity (here indexing genetic ancestry) in genetic risk for CVD and highlights the need to identify ethnicity-specific genetic variants associated with CVD risk.
Assuntos
Aterosclerose/genética , Etnicidade , Lipoproteínas/classificação , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: End-stage renal disease (ESRD) is characterized by profound dyslipidemia and enhanced oxidative stress. The patients also show evidence of exhausted and/or deficient anti-oxidative defense enzymes, one of them being glutathione-S-transferase (GST). This study investigates relationship between GST gene polymorphism and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses in ESRD. DESIGN AND METHODS: GSTM1, T1, and P1 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 160 patients undergoing hemodialysis. LDL and HDL subclasses were separated by gradient gel electrophoresis and biochemical parameters were measured by routine laboratory methods. RESULTS: GSTM1-positive patients had higher proportion of small, dense LDL III particles than those with GSTM1-null genotype (P<0.05). Similarly, GSTP1-Ile/Ile patients had higher proportion of LDL III (P<0.05), but more HDL 2b and less HDL 3a particles than GSTP1-Ile/Val and Val/Val carriers (P<0.05). LDL subclass distribution in smokers with GSTM1-null genotype was shifted towards smaller particles, as compared to GSTM1-positive and GSTM1-null non-smokers. Smokers with GSTP1-Ile/Val and Val/Val genotypes had smaller LDL size than their non-smoking counterparts (P<0.05). Both smokers and non-smokers with GSTP1 Ile/Ile genotype had more LDL III particles than non-smokers carrying Val allele. Non-smokers with GSTP1 Ile/Ile genotype had more HDL 2b subclasses than non-smokers with GSTP1-Ile/Val and Val/Val (P<0.05), but less HDL 3a particles than smokers with GSTP1-Ile/Val and Val/Val genotypes (P<0.05). GSTT1 gene polymorphism had no effect on lipoprotein subclass distributions. CONCLUSIONS: Our results demonstrate significant associations between low activity GST genotypes and proatherogenic lipoprotein particles in hemodialysis patients which might further increase their cardiovascular disease risk.
Assuntos
Estudos de Associação Genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Lipoproteínas/classificação , Polimorfismo Genético , Diálise Renal , Feminino , Humanos , Lipoproteínas HDL , Lipoproteínas LDL , Masculino , Pessoa de Meia-Idade , Fumar/genéticaRESUMO
The objective of this study was to investigate whether differences in diet and in single-nucleotide polymorphisms (SNPs) found in paraoxonase-1 (PON-1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) genes, are associated with oxidative stress biomarkers and consequently with susceptibility of low-density cholesterol (LDL) to oxidation. A multivariate approach was applied to a group of 55 patients according to three biomarkers: plasma antioxidant activity, malondialdehyde and oxidized LDL (oxLDL) concentrations. Individuals classified in Cluster III showed the worst prognoses in terms of antioxidant activity and oxidative status. Individuals classified in Cluster I presented the lowest oxidative status, while individuals grouped in Cluster II presented the highest levels of antioxidant activity. No difference in nutrient intake was observed among the clusters. Significantly higher γ- and δ-tocopherol concentrations were observed in those individuals with the highest levels of antioxidant activity. No single linear regression was statistically significant, suggesting that mutant alleles of the SNPs selected did not contribute to the differences observed in oxidative stress response. Although not statistically significant, the p value of the APO E coefficient for oxLDL response was 0.096, indicating that patients who carry the TT allele of the APO E gene tend to present lower plasma oxLDL concentrations. Therefore, the differences in oxidative stress levels observed in this study could not be attributed to diet or to the variant alleles of PON-1, CETP, HMGCR or APO E. This data supports the influence of γ-tocopherol and δ-tocopherol on antioxidant activity, and highlights the need for further studies investigating APO E alleles and LDL oxidation.
O objetivo deste estudo foi investigar se diferenças na dieta e em polimorfismos de nucleotídeos únicos (SNPs) encontrados no gene da paraoxonase 1 (PON-1), da 3-hidroxi-3-metilglutaril-coenzima A reductase (HMGCR), da proteína de transferência de ésteres de colesterol (CETP) e da apolipoproteina E (APOE) estariam associadas com biomarcadores do estresse oxidativo e, consequentemente, com a suscetibilidade da LDL à oxidação. Técnicas da estatística multivariada foram aplicadas a um grupo de 55 pacientes usando 3 biomarcadores: atividade antioxidante plasmática, concentrações de malondialdeído e LDL oxidada. Indivíduos classificados no cluster III apresentaram um prognóstico negativo em termos de atividade antioxidante e estado oxidativo. Os indivíduos agrupados no cluster I apresentaram o mais baixo nível de estado oxidativo, enquanto que indivíduos no cluster II apresentaram os mais altos níveis de atividade antioxidante. Nenhuma diferença na ingestão de nutrientes foi observada entre os clusters. Concentrações estatísticamente mais altas de γ- e δ-tocoferol foram observadas em indivíduos com mais altos níveis de atividade antioxidante. A regressão linear aplicada não foi estaticamente significativa, sugerindo que os alelos mutantes dos SNPs selecionados não contribuíram para as diferenças nos níveis de estresse oxidativo. Embora não tenha sido estatisticamente significativa, o valor da probabilidade associado ao coeficiente da relação entre ApoE e oxLDL foi de 0,096, indicando que pacientes que carregam o alelo TT da ApoE tendem a apresentar menores concentrações plasmáticas de LDL oxidada. Portanto, as diferenças no estresse oxidativo observadas em nosso estudo não puderam ser atribuídas à dieta e alelos variantes de PON-1, CETP, HMGCR ou ApoE. Nossos dados suportam a influência γ- tocoferol e δ-tocoferol na atividade antioxidante e reforçam a necessidade de mais pesquisas que investiguem a relação entre alelos da Apo E e a oxidação da LDL.
Assuntos
Humanos , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Dieta/classificação , Dislipidemias/diagnóstico , Biomarcadores/análise , Inibidores de Hidroximetilglutaril-CoA Redutases , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Lipoproteínas/classificaçãoRESUMO
OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of atherosclerosis, but routine lipid measurements differ little from those of people without RA. We examined the hypothesis that lipid subclasses determined by nuclear magnetic resonance spectroscopy (NMR) differed in patients with RA compared to controls and are associated with disease activity and the presence of coronary-artery atherosclerosis. METHODS: We measured lipoprotein subclasses by NMR in 139 patients with RA and 75 control subjects. Lipoproteins were classified as large low-density lipoprotein (LDL; diameter range 21.2-27.0 nm), small LDL (18.0-21.2 nm), large high-density lipoprotein (HDL; 8.2-13.0 nm), small HDL (7.3-8.2 nm), and total very low-density lipoprotein (VLDL; >or= 27 nm). All subjects underwent an interview and examination; disease activity was quantified by the 28-joint Disease Activity Score (DAS28) and coronary artery calcification (CAC) was measured with electron-beam computed tomography. RESULTS: Concentrations of small HDL particles were lower in patients with RA (18.2 +/- 5.4 nmol/l) than controls (20.0 +/- 4.4 nmol/l; p = 0.003). In patients with RA, small HDL concentrations were inversely associated with DAS28 (rho = -0.18, p = 0.04) and C-reactive protein (rho = -0.25, p = 0.004). Concentrations of small HDL were lower in patients with coronary calcification (17.4 +/- 4.8 nmol/l) than in those without (19.0 +/- 5.8 nmol/l; p = 0.03). This relationship remained significant after adjustment for the Framingham risk score and DAS28 (p = 0.025). Concentrations of small LDL particles were lower in patients with RA (1390 +/- 722 nmol/l) than in controls (1518 +/- 654 nmol/l; p = 0.05), but did not correlate with DAS28 or CAC. CONCLUSION: Low concentrations of small HDL particles may contribute to increased coronary atherosclerosis in patients with RA.
Assuntos
Artrite Reumatoide/sangue , Calcinose/metabolismo , Doença da Artéria Coronariana/sangue , Lipoproteínas/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Calcinose/complicações , Calcinose/diagnóstico , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Articulações/patologia , Articulações/fisiopatologia , Lipoproteínas/classificação , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Índice de Gravidade de Doença , Tomografia Computadorizada EspiralRESUMO
OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are more insulin resistant and display an atherogenic lipid profile compared with normal women of similar body mass index (BMI). Insulin resistance (IR) at least partially underlies the dyslipidemia of PCOS, but it is unclear whether PCOS status per se confers additional risk. RESEARCH DESIGN AND METHODS: Using a case-control design, we compared plasma lipids and lipoprotein subclasses (using polyacrylamide gel tube electrophoresis) in 70 women with PCOS (National Institutes of Health criteria) and 70 normal women pair matched for age, BMI, and IR (homeostasis model assessment-IR, quantitative insulin sensitivity check index, and the Avignon Index). Subjects were identified as having a (less atherogenic) type A pattern consisting predominantly of large low-density lipoprotein (LDL) subfractions or a (more atherogenic) non-A pattern consisting predominantly of small-dense LDL subfractions. RESULTS: Total, high-density lipoprotein, or LDL cholesterol, or triacylglycerol did not differ between the groups, but very low-density lipoprotein levels (P<0.05) were greater in women with PCOS, whereas a non-A LDL profile was seen in 12.9% compared with 2.9% of controls (P<0.05, chi2). Multiple regression analysis revealed homeostasis model assessment-IR and waist circumference to be independent predictors of very low-density lipoprotein together explaining 40.2% of the overall variance. Logistic regression revealed PCOS status to be the only independent determinant of a non-A LDL pattern (odds ratio 5.48 (95% confidence interval 1.082-27.77; P<0.05). CONCLUSIONS: Compared with women matched for BMI and IR, women with PCOS have potentially important differences in lipid profile with greater very low-density lipoprotein levels and increased rates of a more atherogenic non-A LDL pattern.
Assuntos
Resistência à Insulina/fisiologia , Lipoproteínas/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Colesterol/sangue , Eletroforese em Gel de Poliacrilamida , Feminino , Teste de Tolerância a Glucose , Humanos , Imunoensaio , Insulina/sangue , Lipoproteínas/classificação , Análise de RegressãoRESUMO
BACKGROUND: Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in 142 normolipidemic subjects undergoing coronary angiography. METHODS: Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography. RESULTS: Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concentration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02). CONCLUSION: Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.
Assuntos
Colesterol/metabolismo , Doença da Artéria Coronariana/diagnóstico , Lipoproteínas/sangue , Macrófagos/metabolismo , Idoso , Apolipoproteína A-I/sangue , Células Cultivadas , Constrição Patológica , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Lipoproteínas/classificação , Lipoproteínas HDL2/sangue , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , RiscoRESUMO
BACKGROUND: We assessed racial differences in lipoprotein particle size, a marker of atherosclerosis risk, among women with coronary disease. METHODS: We studied 378 women (33% non-White, predominantly African American) at the baseline visit of the Women's Angiographic Vitamin and Estrogen Trial (WAVE), a multicenter trial of hormone replacement and antioxidant vitamin therapy in postmenopausal women with established coronary artery disease. Average particle sizes for high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein were measured by nuclear magnetic resonance in these women, and angiography was performed at baseline and followup. RESULTS: Adjusted for age, race, diabetes, smoking, blood pressure, and use of lipid-lowering and antihypertensive medications, non-White women had larger LDL particle size (difference .2 nm, 95% CI .1-.3 nm) and HDL particle size (difference.2 nm, 95% CI .1-.2 nm). Neither angiographic disease progression nor survival without myocardial infarction (median follow-up time of 2.8 years) was associated with lipoprotein particle size or race. CONCLUSIONS: Non-White women have a less atherogenic profile of lipoprotein particle sizes than do White women. However, this difference did not affect event-free survival or angiographic progression of coronary atherosclerosis.
Assuntos
Aterosclerose/sangue , Aterosclerose/genética , Doença das Coronárias/sangue , Doença das Coronárias/genética , Lipoproteínas/química , Adulto , Aterosclerose/etnologia , Doença das Coronárias/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Lipoproteínas/classificação , Lipoproteínas/genética , Espectroscopia de Ressonância Magnética , Pessoa de Meia-Idade , Tamanho da Partícula , Pós-Menopausa , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Análise de Sobrevida , Saúde da Mulher/etnologiaRESUMO
OBJECTIVE: This study's objective was to determine if the association between physical activity and lipids and lipoprotein subclasses in postmenopausal women varies by hormone therapy (HT) use. DESIGN: The cross-sectional relationship between physical activity and lipid and lipoprotein subclass relationship was examined before group randomization in 485 postmenopausal (mean age 56.9 [2.9] y) white and African American women from the Woman On the Move through Activity and Nutrition study. This study is a randomized clinical trial designed to test whether a lifestyle intervention will reduce subclinical cardiovascular disease measures. RESULTS: Hormone therapy users (n = 286) were significantly (P < 0.05) younger, less likely to be African American, reported higher levels of physical activity, large very low-density lipoprotein particles (VLDL-P), and medium high-density lipoprotein particles (HDL-P), had a larger mean HDL-P size, and lower levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, small HDL-P, and small VLDL-P than nonusers (n = 196). Physical activity was significantly associated with favorable lipoprotein and lipid levels, regardless of HT use. Some relationships were found to vary significantly by HT use. In nonusers, mean HDL-P and LDL particles (LDL-P) size was significantly larger (P = 0.01 and 0.05, respectively) and total and small LDL-P were significantly lower (both P = 0.02) as activity increased. These relationship were not found in HT users. CONCLUSIONS: Physical activity was significantly related to some lipoprotein subclasses regardless of HT; however, several key lipoprotein subclasses were associated with higher levels of activity only among non-HT users.
Assuntos
Terapia de Reposição de Estrogênios , Exercício Físico/fisiologia , Lipoproteínas/sangue , Pós-Menopausa/sangue , Índice de Massa Corporal , Feminino , Humanos , Modelos Lineares , Lipoproteínas/classificação , Pessoa de Meia-Idade , Análise MultivariadaRESUMO
Os autores ressaltam a importância de uma classificação das dislipidemias aceita pela comunidade científica, o que facilita o estabelecimento do diagnóstico e a melhor terapêutica, bem como o prognóstico das mesmas. Além da propedêutica dos distúrbios lipoprotéicos, são abordados aspectos genéticos das principais dislipidemias.
Assuntos
Masculino , Feminino , Humanos , Hiperlipidemias , Lipoproteínas/análise , Lipoproteínas/classificação , HDL-Colesterol , Hipercolesterolemia/complicações , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etiologiaRESUMO
Apolipoprotein E is a multifunctional protein that is synthesized by the liver and several peripheral tissues and cell types, including macrophages. The protein is involved in the efficient hepatic uptake of lipoprotein particles, stimulation of cholesterol efflux from macrophage foam cells in the atherosclerotic lesion, and the regulation of immune and inflammatory responses. Apolipoprotein E deficiency in mice leads to the development of atherosclerosis and re-expression of the protein reduces the extent of the disease. This review presents evidence for the potent anti-atherogenic action of apolipoprotein E and describes our current understanding of its multiple functions and regulation by factors implicated in the pathogenesis of cardiovascular disease.
Assuntos
Apolipoproteínas E/metabolismo , Arteriosclerose/metabolismo , Animais , Apolipoproteínas E/sangue , Apolipoproteínas E/genética , Arteriosclerose/genética , Arteriosclerose/patologia , Colesterol/sangue , Humanos , Lipoproteínas/sangue , Lipoproteínas/classificação , Lipoproteínas/genética , Lipoproteínas/metabolismo , Macrófagos/metabolismoRESUMO
Platelet-activating factor-acetylhydrolase (PAF-AH) is a lipoprotein-associated phospholipase A2 capable of hydrolyzing platelet-activating factor (PAF) and oxidatively modified phospholipids. We studied the plasma- and lipoprotein-associated PAF-AH activity in patients with primary hypercholesterolemia. Thirty-eight unrelated patients with heterozygous familial hypercholesterolemia (HeteroFH), five patients with homozygous FH (HomoFH), and 33 patients with primary non-FH hypercholesterolemia (NonFH) participated in the study. In all patient groups the plasma PAF-AH activity was significantly elevated compared with 33 normolipidemic controls, the HomoFH having the highest and the NonFH patients showing the lowest enzyme activity. Gradient ultracentrifugation studies showed that this increase is not only due to the elevation in the plasma LDL but also to the increase in the PAF-AH activity associated with each LDL subfraction, being more profound in the small-dense LDL-5. Unlike LDL, no difference in the HDL-associated PAF-AH activity was observed among all groups. Consequently, an altered distribution of enzyme activity among apolipoprotein B (apoB)- and apolipoprotein A-I (apoA-I)-containing lipoproteins is observed in hypercholesterolemic patients, resulting in a significant decrease in the ratio of the HDL-associated PAF-AH to the total plasma enzyme activity compared with controls. This reduction is proportional to the increase of the plasma LDL-cholesterol (LDL-C) levels and consequently to the severity of the hypercholesterolemia. Thus, the ratio of HDL-associated PAF-AH-total plasma enzyme activity may be useful as a potential marker of atherogenicity in subjects with primary hypercholesterolemia.
Assuntos
Apolipoproteínas/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Hiperlipoproteinemia Tipo II/enzimologia , Fosfolipases A/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase , Adulto , Ativação Enzimática , Feminino , Humanos , Hiperlipoproteinemia Tipo II/classificação , Hiperlipoproteinemia Tipo II/genética , Lipoproteínas/sangue , Lipoproteínas/classificação , Lipoproteínas/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfolipases A/metabolismo , Fosfolipases A2 , Índice de Gravidade de DoençaRESUMO
Spontaneously hyperlipidemic (SHL) mice are Japanese wild mice (KOR) with disruption of the apolipoprotein E (Apo E) gene. These mice (KOR-Apoe(shl)) are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis is relatively mild compared with Apo E knockout mice. First, we tested whether this distinction is due to additional mutation of the Apoc1 and/or Apoc2 genes in KOR-Apoe(shl). Southern blot analysis, but found no gross disruption of these genes. Next, we tested whether the phenotypic distinction is due to differences in the genetic background. To this end, we established three lines of congenic SHL mice with a genetic background of C57BL/6, BALB/c or C3H/He, and named them, respectively, C57BL/6.KOR-Apoe(shl) (B6.KOR-Apoe(shl)), BALB/c.KOR-Apoe(shl) (C.KOR-Apoe(shl)) and C3H/He.KOR-Apoe(shl) (C3.KOR-Apoe(shl)). Hypercholesterolemia was most severe in KOR-Apoe(shl) followed the by others as follows; KOR-Apoe(shl)>>C3.KOR-Apoe(shl)>C.KOR-Apoe(shl)>B6.KOR-Apoe(shl). In contrast, atherosclerosis was most severe in B6.KOR Apoe(shl) followed by the others: B6.KOR-Apoe(shl)>C.KOR-Apoe(shl)>>C3.KOR-Apoe(shl)> or =KOR-Apoe(shl). This order, however, did not match that in xanthoma, which was highly prominent in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KORApoe(shl). This order, however, did not match that in xanthoma, which was highly prominant in KOR-Apoe(shl) but mild in B6.KOR-Apoe(shl), C.KOR-Apoe(shl) and C3.KOR-Apoe(shl). These distinctions suggest that the severity of each of the phenotypes is determined by distinct genetic backgrounds which probably are composed of polymorphism of lipid metabolism-related proteins. We found that apolipoprotein A-I is decreased in each SHL strain and polymorphic between B6.KOR-Apoe(shl) and the other strains examined. This polymorphism may be related to the most severe atherosclerosis observed in B6.KOR-Apoe(shl). It is most likely that combination of such polymorphisms is due to the genetic background accountable for phenotype distinctions.
Assuntos
Hiperlipidemias/genética , Camundongos Mutantes/genética , Animais , Arteriosclerose/genética , Arteriosclerose/patologia , Southern Blotting , Western Blotting , Colesterol/sangue , Lipoproteínas/classificação , Camundongos , Fenótipo , Especificidade da Espécie , Xantomatose/genética , Xantomatose/patologiaRESUMO
Human blood plasma samples from 52 subjects were collected and the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein were isolated by serial ultra centrifugation. 600 MHz 1H NMR spectra of the lipoprotein fractions were acquired. The methyl and methylene regions in the spectra of VLDL, LDL and HDL were utilised in further analyses via Kohonen neural networks (KNN) and generative topographic mapping (GTM), two related examples of (unsupervised learning) self-organising feature mapping techniques. Systematic variations in lipoprotein profiles can be substantially visualised through the use of KNN and GTM. The relationship between the sample positions in the Kohonen plot was visualised by surface plots of the corresponding VLDL and HDL cholesterol and VLDL triglyceride contents. The GTM maps of the VLDL and HDL fractions were used to investigate the individual properties of selected samples. A large number of the cancer patients were found clustered in the VLDL GTM map, and GTM map positions of samples in relation to CHD, diabetes and renal failure could be found. Although the study group here considered is heterogeneous in respect to age, sex, type of disease and medications within each defined class, classification of VLDL and HDL data with probabilistic neural network (PNN) was quite successful with respect to the groupings: cancer, CHD, volunteers and other (comprising patients with other diseases). Statistics based on 15 independent sets of PNN calculations gave true positive fractions usually higher than 0.83 and false positive fractions lower than 0.088. Attempts to use the corresponding LDL data and four classes were uniformly poor although some classifications (e.g., volunteer versus CHD) were easily performed.
Assuntos
Doença das Coronárias/sangue , Lipoproteínas/sangue , Neoplasias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/sangue , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas/classificação , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Insuficiência Renal/sangue , Tamoxifeno/farmacologiaRESUMO
Gene transfer and expression of apolipoprotein A-I (apoA-I), the major protein component of high density lipoproteins (HDL), is a potentially attractive method for investigating the effects of apoA-I on atherosclerosis. We constructed a second generation recombinant adenovirus encoding the human apoA-I cDNA. This adenoviral vector or a control vector was injected intravenously into apoE-deficient mice fed a chow diet and low density lipoprotein (LDL) receptor (LDLR)-deficient mice fed Western diet, as well as control wild-type C57BL/6 mice. The mean peak plasma human apoA-I concentrations were 235, 324, and 276 mg/dL in apoE-deficient, LDLR-deficient, and wild-type mice, respectively. Human apoA-I concentrations decreased rapidly in apoE-deficient mice and were barely detectable 6 weeks after injection. In contrast, substantially higher levels of human apoA-I were sustained in LDLR-deficient mice. In wild-type mice, human apoA-I levels decreased more rapidly than in LDLR-deficient mice, but could still be detected in plasma for up to 8 months after virus injection. In apoE-deficient mice a substantial fraction of human apoA-I was found associated with triglyceride (TG)-rich lipoproteins; in contrast, in LDLR-deficient and wild-type mice the majority of human apoA-I was found in the HDL fraction. Finally, expression of human apoA-I caused a transient but significant increase in triglyceride levels in all three mouse models. In summary: 1) a second generation recombinant adenovirus resulted in high-level expression of human apoA-I in mice; 2) significantly higher levels of human apoA-I persisted for a longer time in LDLR-deficient mice compared with apoE-deficient mice; and 3) substantial human apoA-I was found associated with TG-rich lipoproteins in apoE-deficient but not LDLR-deficient mice.
Assuntos
Apolipoproteína A-I/genética , Arteriosclerose/genética , Adenoviridae/genética , Animais , Apolipoproteína A-I/sangue , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Arteriosclerose/sangue , Arteriosclerose/etiologia , Modelos Animais de Doenças , Expressão Gênica , Técnicas de Transferência de Genes , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Lipoproteínas/química , Lipoproteínas/classificação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de LDL/deficiência , Receptores de LDL/genéticaRESUMO
Data on plasma concentrations of tocopherols and the major carotenoids in adults aged > or = 65 y, particularly in those > 80 y, are sparse. In the current study retinol, tocopherol (alpha- and gamma-tocopherols), and carotenoid (lutein/zeaxanthin, cryptoxanthins, lycopene, and alpha- and beta-carotene) concentrations were determined in 638 subjects, 230 men (aged 75 +/- 5 y) and 408 women (76 +/- 6 y), of the Framingham Heart Study. All subjects were free of clinical evidence of cardiovascular disease and cancer. Percentile ranges were comparable with those established in younger cohorts. Moreover, women had significantly higher plasma alpha-tocopherol and plasma and lipoprotein concentrations of beta-cryptoxanthin and alpha- and beta-carotene than did men. Lycopene concentrations were inversely correlated with age and lowest among subjects > or = 80 y. Total intakes (diet+supplements) of vitamin C and vitamin E, but not dietary intakes alone, were positively associated with plasma alpha-tocopherol and inversely associated with gamma-tocopherol concentrations. In multivariate analyses, plasma cholesterol and triacylglycerol concentrations and total intake of vitamins E and C predicted 64% and 55% of the plasma alpha-tocopherol concentrations in men and women, respectively. Important predictors for the majority of carotenoids included plasma cholesterol concentration, body mass index (negative effect), and smoking status (negative effect); for lycopene concentration they included cholesterol concentration and age (negative effect). In summary, percentile ranges and lipoprotein distributions were comparable with those established in younger cohorts, suggesting that overall antioxidant status is not altered in people between the ages of 67 and 96 y.
Assuntos
Carotenoides/análise , Lipoproteínas/química , Vitamina A/sangue , Vitamina E/análise , Idoso , Idoso de 80 Anos ou mais , Carotenoides/sangue , Estudos de Coortes , Criptoxantinas , Feminino , Seguimentos , Humanos , Lipoproteínas/classificação , Luteína/análise , Luteína/sangue , Licopeno , Masculino , Caracteres Sexuais , Vitamina E/sangue , Xantofilas , beta Caroteno/análogos & derivados , beta Caroteno/análise , beta Caroteno/sangueRESUMO
To further elucidate the incidence and potential mechanism of asparaginase-associated lipid abnormalities in children with acute lymphoblastic leukemia (ALL), we serially obtained fasting lipid and lipoprotein studies on 38 of the 43 consecutively diagnosed children with ALL before, during, and after asparaginase therapy. We also evaluated a second population of 30 long-term survivors of childhood ALL; a fasting lipid and lipoprotein profile was obtained once at study entry. The mean peak triglyceride level during asparaginase of 465 mg/dL (standard deviation [SD] 492) was significantly higher (P = .003) than the level of 108 mg/dL (SD 46) before the initiation of asparaginase therapy. Sixty-seven percent of the newly diagnosed patients had fasting triglyceride levels greater than 200 mg/dL during asparaginase therapy; 15 patients (42%) had levels greater than 400 mg/ dL, 7 with levels greater than 1,000 mg/dL. The incidence of hypertriglyceridemia did not vary by type of asparaginase or risk status of ALL (defined by white blood cell count and age). None of the 7 patients with triglyceride levels greater than 1,000 mg/dL developed pancreatitis. In contrast, 4 of the 13 patients without triglyceride elevation developed pancreatitis; 3 of the 4 patients had fasting studies at the height of their abdominal pain. Nuclear magnetic resonance analysis of lipid subclasses showed a significant increase in the smaller, denser forms of very low density lipoprotein (VLDL) and negligible chylomicron fraction in a subset of patients with marked triglyceride elevation. Lipoprotein lipase activity was consistently above normative values for all levels of triglyceride and could not be explained by obesity or hyperglycemia. Apolipoprotein B(100) levels increased during asparaginase therapy, although the mechanism of this remains unclear. LDL reciprocally decreased with increased VLDL during asparaginase therapy. After asparaginase therapy, triglyceride levels (mean, 73 mg/dL [SD 33]) were significantly lower than levels obtained during asparaginase therapy. Triglyceride levels for survivors did not differ from the normal range or postasparaginase levels in the newly diagnosed patients. These data show a striking temporal association between asparaginase therapy and hypertriglyceridemia. Changes in cholesterol, in contrast, were not temporally related to asparaginase treatment. Cholesterol levels were elevated (>200 mg/dL) in 20% of the patients after asparaginase, which may be due to continued treatment with corticosteroids. The mean cholesterol level of long-term survivors of 177 mg/dL was significantly higher than the norm (P = .045). High-density lipoprotein (HDL) levels were significantly lower than normal at all time periods and for both populations; 25% of survivors had HDL levels less than 35 mg/dL. We conclude that modifications in asparaginase therapy are not necessary. In cases of triglyceride elevation greater than 2,000 mg/dL when the risk of pancreatitis is increased, close clinical monitoring is imperative. Larger studies are needed to determine the incidence of dyslipidemia in long-term survivors of ALL as well as the relationship between lipid abnormalities and other late effects of treatment, notably obesity and cardiomyopathies.