Plasma PLTP activity is inversely associated with HDL-C levels

Chen, Xueying; Sun, Aijun; Mansoor, Ather; Zou, Yunzeng; Ge, Junbo; Lazar, Jason

doi:10.1186/1743-7075-6-49

Cited by 20 publications

(14 citation statements)

References 36 publications

(41 reference statements)

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“…Human plasma PLTP activity is inversely associated with HDL levels 11–13 . Moreover, human genome-wide association studies also suggest that plasma HDL levels are associated with variation in the PLTP locus 9 .…”

Section: Introductionmentioning

confidence: 99%

Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism

Jiang

Yazdanyar

Lou

et al. 2015

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Objective Phospholipid transfer protein (PLTP) is highly expressed in adipose tissues. Thus, the effect of adipose tissue PLTP on plasma lipoprotein metabolism was examined. Approach and Results we crossed PLTP-Flox-ΔNeo and adipocyte protein 2 (aP2)-Cre transgenic mice to create PLTP-Flox-ΔNeo/aP2-Cre mice that have a 90 and a 60% reduction in PLTP mRNA in adipose tissue and macrophages, respectively. PLTP ablation resulted in a significant reduction in plasma PLTP activity (22%) and in high-density lipoprotein (HDL), cholesterol (21%), phospholipid (20%), and apolipoprotein A-I (apoA-I; 33%) levels, but had no effect on non-HDL levels in comparison with those of PLTP-Flox-ΔNeo controls. To eliminate possible effects of PLTP ablation by macrophages, we lethally irradiated PLTP-Flox-ΔNeo/aP2-Cre mice and PLTP-Flox-ΔNeo mice, and then transplanted wild-type mouse bone marrow into them to create wild-type (WT)→PLTP- Flox-ΔNeo/aP2-Cre and WT→PLTP-Flox-ΔNeo mice. Thus, we constructed a mouse model (WT→PLTP-Flox-ΔNeo/aP2-Cre) with PLTP deficiency in adipocytes but not in macrophages. These knockout mice also showed significant decreases in plasma PLTP activity (19%) and cholesterol (18%), phospholipid (17%), and apoA-I (26%) levels. To further investigate the mechanisms behind the reduction in plasma apoA-I and HDL lipids, we measured apoA-I-mediated cholesterol efflux in adipose tissue explants and found that endogenous and exogenous PLTP significantly increased cholesterol efflux from the explants. Conclusions Adipocyte PLTP plays a small but significant role in plasma PLTP activity and promotes cholesterol efflux from adipose tissues.

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Section: Introductionmentioning

confidence: 99%

Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism

Jiang

Yazdanyar

Lou

et al. 2015

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“…14,15 In a cohort of Chinese patients with or without coronary artery disease, plasma PLTP activity was recently shown to associate nega-tively with plasma HDL and apoAI levels and positively with plasma triglycerides, apoB levels, and apoE levels. 16 In a large cross-sectional study, high PLTP in diabetics was associated with significant changes in HDL size distribution, as well as with an increase in apoB-containing lipoprotein level. 17 In recent genome-wide analyses, a number of loci were found to associate with HDL cholesterol and triglycerides; among them, one was localized at the PLTP gene.…”

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Worsening of Diet-Induced Atherosclerosis in a New Model of Transgenic Rabbit Expressing the Human Plasma Phospholipid Transfer Protein

Masson

Deckert

Gautier

et al. 2011

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Objective-Plasma phospholipid transfer protein (PLTP) is involved in intravascular lipoprotein metabolism. PLTP is known to act through 2 main mechanisms: by remodeling high-density lipoproteins (HDL) and by increasing apolipoprotein (apo) B-containing lipoproteins. The aim of this study was to generate a new model of human PLTP transgenic (HuPLTPTg) rabbit and to determine whether PLTP expression modulates atherosclerosis in this species that, unlike humans and mice, displays naturally very low PLTP activity. Methods and Results-In HuPLTPTg rabbits, the human PLTP cDNA was placed under the control of the human eF1-␣ gene promoter, resulting in a widespread tissue expression pattern and in increased plasma PLTP. The HuPLTPTg rabbits showed a significant increase in the cholesterol content of the plasma apoB-containing lipoprotein fractions, with a more severe trait when animals were fed a cholesterol-rich diet. In contrast, HDL cholesterol level was not modified in HuPLTPTg rabbits. Formation of aortic fatty streaks was increased in hypercholesterolemic HuPLTPTg animals as compared with nontransgenic littermates. Key Words: atherosclerosis Ⅲ lipoproteins Ⅲ metabolism Ⅲ transgenic models H uman plasma contains 2 distinct lipid transfer proteins (cholesteryl ester transfer protein [CETP] and phospholipid transfer protein [PLTP]) that promote the rapid exchange of lipid species between circulating lipoproteins, as well as between circulating lipoproteins and cells. 1 Although most reported data agree that the putative implication of CETP in lipoprotein metabolism and atherosclerotic process mostly concerns the net transfer of cholesteryl esters from antiatherogenic high-density lipoproteins (HDL) to potentially atherogenic apolipoprotein (apo) B-containing lipoproteins, 1 the precise function of PLTP and its consequences in terms of atherogenesis remain a matter of debate. PLTP was identified initially for its ability to promote the transfer of phospholipids from triglyceride-rich lipoproteins to HDL in the postprandial phase. 2 Subsequent studies reported that PLTP is also a key player in the HDL conversion process, leading to the emergence of large and small HDL products. 3,4 Recently, PLTP in human plasma was shown to reside mainly on lipid-poor complexes in association with proteins linked to immunity and inflammation, suggesting that the biological function of PLTP is rather complex in nature. 5 In support of this view, PLTP expression in the mouse was found to increase the production of apoB-containing lipoproteins by the liver 6 and intestine, 7 to decrease very low density lipoprotein (VLDL) catabolism, 8 to reduce the antioxidant protection of atherogenic lipoproteins, 9,10 to trigger inflammation, 11 and to promote the association of lipopolysaccharides with circulating lipoproteins. 12 All these properties have long been shown to influence the atherosclerotic process, whether acting individually or in a combined manner. Conclusion-HumanHigh plasma PLTP concentrations were earlier reported in diabetic...

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“…In human studies, PLTP activity is inversely associated with HDL levels 8, 9 . PLTP mediates HDL remodeling and enlargement 10, 11 .…”

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Liver-Specific Phospholipid Transfer Protein Deficiency Reduces High-Density Lipoprotein and Non–High-Density Lipoprotein Production in Mice

Yazdanyar

Wei

Jin

2013

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Objectives The liver is one of the critical organs for lipoprotein metabolism and a major source for phospholipid transfer protein (PLTP) expression. The effect of liver-specific PLTP deficiency on plasma lipoprotein production and metabolism was investigated. Approach and Results We created a liver-specific PLTP deficient mouse model. We measured plasma high density lipoprotein (HDL) and apolipoprotein B-containing lipoprotein (BLp, or non-HDL) levels and their production rates. We found that hepatic ablation of PLTP leads to a significant decrease in plasma PLTP activity, HDL-lipids, non-HDL-lipids, apoA-I, and apoB levels. In addition, nuclear magnetic resonance (NMR) examination of lipoproteins showed that the deficiency decreases HDL and BLp particle numbers, as well as VLDL particle size which were confirmed by electron microscopy. Moreover, HDL particles from the deficient mice are lipid-poor ones. To unravel the mechanism, we evaluated the apoB and triglyceride production rates. We found that hepatic PLTP deficiency significantly decreases apoB and triglyceride secretion rates. To investigate the role of liver PLTP on HDL production, we set up primary hepatocyte culture studies and found that the PLTP deficient hepatocytes produce less nascent HDL. Furthermore, we found that exogenous PLTP promotes nascent HDL production through an ABCA1-mediated pathway. Conclusions Liver-specific PLTP deficiency significantly reduces plasma HDL and BLp levels. Reduction of production rates of both particles is one of the mechanisms.

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Plasma PLTP activity is inversely associated with HDL-C levels

Cited by 20 publications

References 36 publications

Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism

Adipocyte Phospholipid Transfer Protein and Lipoprotein Metabolism

Worsening of Diet-Induced Atherosclerosis in a New Model of Transgenic Rabbit Expressing the Human Plasma Phospholipid Transfer Protein

Liver-Specific Phospholipid Transfer Protein Deficiency Reduces High-Density Lipoprotein and Non–High-Density Lipoprotein Production in Mice

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