Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A‐V deficiency due to a novel mutation in the <i>APOA5</i> gene

Oliva, Claudio Priore; Carubbi, Francesca; Schaap, Frank G.; Bertolini, Stefano; Calandra, Sebastiano

doi:10.1111/j.1365-2796.2007.01912.x

Cited by 49 publications

(35 citation statements)

References 32 publications

(34 reference statements)

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“…A greater blood TG level is associated with a lower blood HDLcholesterol level. An apo A-V deficiency might delay TG hydrolysis and reduce the availability of the surface components of TG-rich lipoproteins (which contribute to HDL-cholesterol formation), thereby leading to a decreased formation of HDL cholesterol [30]. Additionally, apo A-V-deficient mice have shown decreased lipoprotein lipase activity and the accumulation of larger VLDL particles [31], which are precursors of small, dense LDL, an independent predictor of coronary artery disease [32].…”

Section: Discussionmentioning

confidence: 98%

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia

et al. 2015

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Section: Discussionmentioning

confidence: 98%

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia

et al. 2015

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“…30,31 Disruption of TRL metabolism. 37 Increased TG levels, no significant changes in plasma HDL-C levels. 38 Decreased plasma TG levels but no significant changes in plasma HDL-C Rare and common variants associated with high TG.…”

Section: Genesmentioning

confidence: 99%

Mendelian Disorders of High-Density Lipoprotein Metabolism

Oldoni

Sinke

Kuivenhoven

2014

Circulation Research

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High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL cholesterol levels through their roles in HDL and triglyceride metabolism. Using this information from both human and animal studies, it is discussed how HDL is produced, remodeled in the circulation, affected by factors that control the metabolism of triglyceride-rich lipoproteins, how it helps maintain cellular cholesterol homeostasis, and, finally, how it is catabolized. It can be concluded that HDL cholesterol as a trait is genetically heterogeneous, with as many as 40 genes involved. In most cases, only heterozygotes of gene variants are known, and HDL cholesterol as a trait is inherited in an autosomal-dominant manner. Only 3 Mendelian disorders of HDL metabolism are currently known, which are inherited in an autosomal-recessive mode. an overview of the knowledge that has been obtained through mutations (or targeted disruption) of these genes and illustrates the current molecular details of HDL anabolism, conversion, and catabolism. The Table summarizes how mutations in these genes may affect atheroclerosis. TerminologyDefinitions of HDL and HDL-C The mobilization of cellular cholesterol by HDL, the transport of cholesterol by HDL in the circulation, and the hepatic uptake of HDL-C are generally considered as key to the function of this lipoprotein class. However, from a biochemical perspective, HDL-C is a mere figure indicating how much cholesterol is carried by the pool of HDL in blood. Unfortunately, the terms HDL and HDL-C are often used interchangeably. This leads to confusion and sometimes wrong interpretations. In the lay literature, HDL-C is often typed as the good cholesterol, suggesting that cholesterol is beneficial as long as it is in HDL that diverts from the multiple functions that are attributed to HDL that has little if nothing to do with its cholesterol component. In this review, HDL is used when either the particle or the pool of circulating HDL is meant, whereas HDL-C refers to the free cholesterol (FC) and cholesteryl ester (CE) carried by HDL in the circulation. HDL deficiency indicates that HDL and, therefore, HDL-C are (close to) absent. In an attempt to be comprehensive, we have combined genetic insights from both animal and human studies. Finally, the terms hypoalphalipoproteinemia and hyperalphalipoproteinemia are used when HDL-C concentrations are <10th percentile or >90th percentile for age and sex, respectively. Reverse Cholesterol Transport and Cellular Cholesterol HomeostasisReverse cholesterol transport is generally used to describe the transport of cholesterol by HDL from the vascular wall to the liver for excretion into bile as neutral sterol or bile acid. Despite ≈50 years of research, there is, as of yet, little evidence that HDL can transport cholesterol from the vessel...

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“…Relevance for TG homeostasis was initially demonstrated using genetically engineered mice: Overexpression of human apoAV decreased plasma TG by 64%, while apoa5-deficient mice had 4-fold increased plasma TG levels (1). In humans, it was furthermore shown that variation at the APOA5 gene locus was associated with TG levels (2-4), while complete apoAV deficiency was associated with severe hypertriglyceridemia (5,6). Combined, these data suggested that plasma levels of apoAV are in general inversely correlated with TG levels.…”

mentioning

confidence: 99%

Plasma apolipoprotein AV levels in mice are positively associated with plasma triglyceride levels

Vaessen

Dallinga‐Thie

Ross

et al. 2009

Journal of Lipid Research

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Apolipoprotein AV (apoAV) overexpression causes a decrease in plasma triglyceride (TG) levels, while deficiency of apoAV causes hypertriglyceridemia in both men and mice. However, contrary to what would be expected, plasma apoAV and TG levels in humans are positively correlated. To address this apparent paradox, we determined plasma apoAV levels in various mouse models with median TG levels ranging from 30 mg/dl in wild-type mice to 2089 mg/dl in glycosylphosphatidylinositol-anchored HDL binding protein 1-deficient mice. The data show that apoAV and TG levels are positively correlated in mice (r 5 10.798, P , 0.001). In addition, we show that LPL gene transfer caused a simultaneous decrease in TG and apoAV in LPL-deficient mice. The combined data suggest that apoAV levels follow TG levels due to an intimate link between the apoAV molecule and TG-rich lipoproteins, comprising both secretion and removal of these lipoproteins. Taken together, the data suggest that higher plasma apoAV levels reflect an increased demand for plasma TG hydrolysis under normal physiological conditions.-Vaessen, S. Since its discovery in 2001, apolipoprotein AV (apoAV) has been postulated as a key regulator of plasma triglyceride (TG) levels (1). Relevance for TG homeostasis was initially demonstrated using genetically engineered mice: Overexpression of human apoAV decreased plasma TG by 64%, while apoa5-deficient mice had 4-fold increased plasma TG levels (1). In humans, it was furthermore shown that variation at the APOA5 gene locus was associated with TG levels (2-4), while complete apoAV deficiency was associated with severe hypertriglyceridemia (5, 6). Combined, these data suggested that plasma levels of apoAV are in general inversely correlated with TG levels. However, we and others subsequently showed that plasma apoAV and TG levels are, unexpectedly, positively correlated in patients with type 2 diabetes and in the general population (7-11). Considering the suggested negative correlation between plasma apoAV and TG in mice, based on the overexpression models, these subsequent observations in humans have led several investigators to suggest an inherent difference between humans and mice (10-12). This despite the fact that the phenotypic presentation of complete apoAV deficiency in mice and humans is similar (1, 5). Moreover, in mice with endotoxemia (13) or in rats fed PUFAs (14), semiquantification of apoAV levels by immunoblotting also suggested a positive correlation with TG levels. In addition, Nelbach et al. (15) recently showed a positive correlation between plasma apoAV and TG concentrations in mice overexpressing human apoAV. In this study, we further addressed this hypothesis by determining the relationship between plasma apoAV and TG levels in wild-type mice and various genetically engineered mouse models that are characterized by a wide range of elevated levels of plasma triglycerides. METHODS Mouse modelsTo determine the association between plasma apoAV and TG levels in mice, we collected plasma samples from ...

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Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A‐V deficiency due to a novel mutation in the APOA5 gene

Cited by 49 publications

References 32 publications

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia

Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduces fasting triglycerides and enhances apolipoprotein A-V levels in non-diabetic subjects with hypertriglyceridemia

Mendelian Disorders of High-Density Lipoprotein Metabolism

Plasma apolipoprotein AV levels in mice are positively associated with plasma triglyceride levels

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