Analysis of lipid transfer activity between model nascent HDL particles and plasma lipoproteins: implications for current concepts of nascent HDL maturation and genesis

Bailey, Dana; Ruel, Isabelle L.; Hafiane, Anouar; Cochrane, Haley; Iatan, Iulia; Jauhiainen, Matti; Ehnholm, Christian; Krimbou, Larbi; Genest, Jacques

doi:10.1194/jlr.m001875

Cited by 27 publications

(28 citation statements)

References 40 publications

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“…It has been shown that apolipoprotein B lipoproteins can be direct acceptors of free cholesterol released from cells in vitro. 16 The importance of preb-1 HDL as a key mediator of ABCA1-mediated cholesterol efflux from macrophages in IR states was recently demonstrated by Attia et al, 17 who measured cholesterol efflux capacity in ABCA1-expressing J774 cells incubated with sera from obese subjects with insulin resistance. They concluded that the preb-1 HDL levels were the major determinants of efflux capacity.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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Objective: In vitro measurements of cholesterol efflux from macrophages have recently been shown to associate with cardiovascular risk. We investigated whether cholesterol efflux from macrophages incubated with plasmas from overweight/ obese subjects with metabolic syndrome was influenced by the presence of insulin resistance. Methods: Plasmas were obtained from 47 men and women with metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22 insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose tolerance test). Activated human macrophage THP-1 cells in which cholesterol had been radiolabelled were incubated with the subjects' plasmas to allow calculation of % cholesterol efflux. Results: Body mass index and waist measurements, as well as plasma lipid levels, did not differ between the two groups. Homeostatic model assessment-insulin resistance value as well as plasma insulin and leptin concentrations were higher in IR subjects. Cholesterol efflux was found to be significantly greater with plasmas from IR subjects (9.1%) than from IS subjects (6.7%) (P ¼ 0.005). Further, cholesterol efflux was significantly inversely associated with insulin sensitivity index (Po0.001), directly with arterial insulin concentration (Po0.001) and directly with cholesteryl ester transfer protein (CETP) mass (P ¼ 0.044). Conclusion: Plasmas from overweight subjects with insulin resistance induced greater in vitro cholesterol efflux compared with IS subjects. Efflux inversely correlated with insulin sensitivity suggesting an increase in reverse cholesterol transport in the IR state that may lead to greater transfer of cholesterol to apoB lipoproteins from high-density lipoproteins via CETP as a factor in the association between IR and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

et al. 2011

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“…Two forms of functionally defi ned PLTP are found in the plasma ( 19 ): an "active" form that can transfer triglyceride-rich phospholipids from VLDLs and chylomicrons to HDL ( 20,21 ), and an "inactive" form that lacks this capability. Between 50 and 90% of total measures, baseline demographic/clinical characteristics, and genetic variants in the PLTP region.…”

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confidence: 99%

PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity

Kim

Burt

Ranchalis

et al. 2015

Journal of Lipid Research

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Cholesterol carried on HDL (HDL-C) has long been believed to be cardioprotective, based on consistent epidemiologic fi ndings of an inverse relationship between incident CVD and HDL-C levels in subjects healthy at baseline ( 1, 2 ). Estimates from the Framingham Heart Study found that risk of myocardial infarction (MI) increased by 25% for each 5 mg/dl decrease in HDL-C below median values of HDL-C for both healthy men and women ( 2 ). Similar fi ndings of the cardioprotective effects of HDL-C have also been reported in subjects with CVD at baseline ( 3 ).In confl ict with these epidemiologic fi ndings, recent attempts to establish a causal relationship between HDL-C Abstract Recent studies have failed to demonstrate a causal cardioprotective effect of HDL cholesterol levels, shifting focus to the functional aspects of HDL. Phospholipid transfer protein (PLTP) is an HDL-associated protein involved in reverse cholesterol transport. This study sought to determine the genetic and nongenetic predictors of plasma PLTP activity (PLTPa), and separately, to determine whether PLTPa predicted carotid artery disease (CAAD). PLTPa was measured in 1,115 European ancestry participants from a casecontrol study of CAAD. A multivariate logistic regression model was used to elucidate the relationship between PLTPa and CAAD. Separately, a stepwise linear regression determined the nongenetic clinical and laboratory characteristics that best predicted PLTPa. A fi nal stepwise regression considering both nongenetic and genetic variables identifi ed the combination of covariates that explained maximal PLTPa variance. PLTPa was signifi cantly associated with CAAD (7.90 × 10 ؊ 9 ), with a 9% decrease in odds of CAAD per 1 unit increase in PLTPa (odds ratio = 0.91). Triglyceride levels ( P = 0.0042), diabetes ( P = 7.28 × 10 ؊ 5 ), paraoxonase 1 (PON1) activity ( P = 0.019), statin use ( P = 0.026), PLTP SNP rs4810479 ( P = 6.38 × 10 ؊ 7 ), and PCIF1 SNP rs181914932 ( P = 0.041) were all signifi cantly associated with PLTPa. PLTPa is signifi cantly inversely correlated with CAAD. Furthermore, we report a novel association between PLTPa and PON1 activity, a known predictor of

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“…It is generally accepted that nascent HDLs acquire unesterified cholesterol and associate with LCAT, leading to cholesterol esterification and their conversion to mature HDL. 34 Our studies provide evidence for another mechanism by which nascent HDLs can enter the mature HDL pool that is enhanced by PLTP-mediated particle remodeling.…”

Section: Discussionmentioning

confidence: 64%

Impact of Phospholipid Transfer Protein on Nascent High-Density Lipoprotein Formation and Remodeling

Wroblewski

Webb

et al. 2014

ATVB

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Objective Phospholipid transfer protein (PLTP), which binds phospholipids and facilitates their transfer between lipoproteins in plasma, plays a key role in lipoprotein remodeling but its influence on nascent HDL formation is not known. The effect of PLTP over-expression on apoA-I lipidation by primary mouse hepatocytes was investigated. Approach and Results Over-expression of PLTP through an adenoviral vector markedly affected the amount and size of lipidated apoA-I species that were produced in hepatocytes in a dose-dependent manner, ultimately generating particles that were smaller than 7.1 nm but larger than lipid-free apoA-I. These < 7.1 nm small particles generated in the presence of over-expressed PLTP were incorporated into mature HDL particles more rapidly than apoA-I both in vivo and in vitro, and were less rapidly cleared from mouse plasma than lipid-free apoA-I. The < 7.1 nm particles promoted both cellular cholesterol and phospholipid efflux in an ATP-binding cassette transporter A1 (ABCA1) dependent manner, similar to apoA-I in the presence of PLTP. Lipid-free apoA-I had a greater efflux capacity in the presence of PLTP than in the absence of PLTP, suggesting that PLTP may promote ABCA1-mediated cholesterol and phospholipid efflux. These results indicate that PLTP alters nascent HDL formation by modulating the lipidated species as well as promoting the initial process of apoA-I lipidation. Conclusions Our findings suggest that PLTP exerts significant effects on apoA-I lipidation and nascent HDL biogenesis in hepatocytes by promoting ABCA1-mediated lipid efflux and the remodeling of nascent HDL particles.

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Analysis of lipid transfer activity between model nascent HDL particles and plasma lipoproteins: implications for current concepts of nascent HDL maturation and genesis

Cited by 27 publications

References 40 publications

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

Cholesterol efflux from macrophages is influenced differentially by plasmas from overweight insulin-sensitive and -resistant subjects

PLTP activity inversely correlates with CAAD: effects of PON1 enzyme activity and genetic variants on PLTP activity

Impact of Phospholipid Transfer Protein on Nascent High-Density Lipoprotein Formation and Remodeling

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