Quantification of human plasma phospholipid transfer protein (PLTP): relationship between PLTP mass and phospholipid transfer activity

Huuskonen, Jarkko; Ekström, Minna; Tahvanainen, Esa; Vainio, Anu; Metso, Jari; Pussinen, Pirkko J.; Ehnholm, Christian; Olkkonen, Vesa M.; Jauhiainen, Matti

doi:10.1016/s0021-9150(99)00429-3

Cited by 65 publications

(88 citation statements)

References 41 publications

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“…As a result, we observed relatively small ranges in plasma apoB and cholesterol levels (Table 1), which could have obscured a relationship between PLTP activity and LDL cholesterol levels. Positive correlations with plasma triglycerides and cholesterol have been reported in a Finnish population study (44), but this could not be replicated in the present study, where correlations with triglycerides (r ϭ 0.10, NS) and cholesterol (r ϭ 0.00, NS) were only weak or absent.…”

Section: Discussioncontrasting

confidence: 99%

Plasma Phospholipid Transfer Protein Activity Is Decreased in Type 2 Diabetes During Treatment With Atorvastatin

Dallinga‐Thie

Tol²,

Hashimoto³

et al. 2006

Diabetes

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Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbA 1c , glucose, and apoE (all P < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg atorvastatin: ؊8.3%, P < 0.05; 80 mg atorvastatin: ؊12.1%, P < 0.002). Plasma apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was strongly related to the decrease in PLTP activity (r ‫؍‬ 0.565, P < 0.001). The change in apoE remained the sole determinant of the change in PLTP activity in a multivariate model. The activity of PLTP in type 2 diabetes is decreased by atorvastatin. The association between the decrease in PLTP activity and apoE during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation.

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Section: Discussioncontrasting

confidence: 99%

Plasma Phospholipid Transfer Protein Activity Is Decreased in Type 2 Diabetes During Treatment With Atorvastatin

Dallinga‐Thie

Tol²,

Hashimoto³

et al. 2006

Diabetes

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“…As expected, PLTP activity was higher in huCETPtg/huPLTPtg mice than in the huCETPtg mice ( Table 1). The human PLTP mass measured in huCETPtg/huPLTPtg mice is within the range of reported plasma PLTP concentrations in humans (17,24,25). In contrast to what has been reported in humans (26,27), in our mice PLTP activity correlates with human PLTP mass.…”

Section: Downloaded Fromsupporting

confidence: 78%

Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion

Lie¹,

Crom

Gent³

et al. 2002

Journal of Lipid Research

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Two lipid transfer proteins are active in human plasma, cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). Mice by nature do not express CETP. Additional inactivation of the PLTP gene resulted in reduced secretion of VLDL and subsequently in decreased susceptibility to diet-induced atherosclerosis. The aim of this study is to assess possible effects of differences in PLTP expression on VLDL secretion in mice that are proficient in CETP and PLTP. We compared human CETP transgenic (huCETPtg) mice with mice expressing both human lipid transfer proteins (huCETPtg/huPLTPtg). Plasma cholesterol in huCETPtg mice was 1.5-fold higher compared with huCETPtg/huPLTPtg mice ( P Ͻ 0.001). This difference was mostly due to a lower HDL level in the huCETPtg/huPLTPtg mice, which subsequently could lead to the somewhat decreased CETP activity and concentration that was found in huCETPtg/huPLTPtg mice ( P Ͻ 0.05). PLTP activity was 2.8-fold increased in these animals ( P Ͻ 0.001). The human PLTP concentration was 5 g/ml. Moderate overexpression of PLTP resulted in a 1.5-fold higher VLDL secretion compared with huCETPtg mice ( P Ͻ 0.05). The composition of nascent VLDL was similar in both strains. These results indicate that elevated PLTP activity in huCETPtg mice results in an increase in VLDL secretion. In addition, PLTP overexpression decreases plasma HDL cholesterol as well as CETP. Phospholipid transfer protein (PLTP) is an important modulator of plasma HDL levels, size, and composition (1-5). HDL is considered to protect against atherosclerosis by transporting cellular cholesterol from cells in the arterial wall to the liver for further excretion via the bile, as well as by exerting anti-inflammatory and anti-oxidant effects (6-8).The role of PLTP in atherosclerosis was recently evaluated in PLTP deficient mice (5). PLTP deficiency in hyperlipidemic mouse models resulted in decreased atherosclerosis. In vitro experiments with cultured hepatocytes from PLTP deficient mice revealed a defect in VLDL secretion. These effects on VLDL secretion provided an explanation for the decreased atherosclerosis found in PLTP deficient mice (5).Earlier we reported anti-atherogenic properties in mice overexpressing human PLTP (huPLTPtg). Despite lower HDL levels, plasma from these mice is more effective in preventing in vitro accumulation of cholesterol by macrophages and is able to generate more pre ␤ -HDL (3, 9). Studies in mice with adenovirus-mediated overexpression of human PLTP showed similar effects on HDL subclass distribution (10, 11).Thus, depending on the metabolic setting, PLTP may have anti-or pro-atherogenic properties that require further investigation. Presently, we aimed to evaluate whether VLDL secretion is affected by variations in PLTP activity. For this purpose, we crossbred transgenic mice for human CETP (huCETPtg) with huPLTPtg mice (9) and obtained huCETPtg/huPLTPtg mice. These mice provide a unique model to study the role of PLTP in VLDL metabolism in the presence of CETP, whi...

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“…22 It is also suggested that majority of the PLTP mass exists in the inactive form in the circulation in healthy subjects. 16,17 We obtained the data regarding PLTP activity in a sample of subjects, and the results indicated that the concentration of serum PLTP mass did not correlate with its activity. Thus, the inverse association between PLTP mass and CHD found in this study may not be solely attributed to the phospholipid transfer activity of PLTP.…”

Section: Discussionmentioning

confidence: 99%

“…17 They found that the low PLTP concentration in hypoalphalipoproteinemia was because of a lack of inactive PLTP. Dyslipidemic states, such as low HDL-C or elevated TG, 16,22 or intravenous infusion of apo A-I/phosphatidylcholine discs, which increases the plasma pre--apo A-I and HDL-C concentrations, 27 were demonstrated to modify the distribution of active and inactive pools of PLTP. It is, therefore, necessary to conduct further research to elucidate the mechanisms involved in the existence of inactive PLTP, with regard to its function in lipoprotein metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] Sandwich enzyme-linked immunosorbent assay with 2 monoclonal antibodies to human PLTP has been recently introduced to assay PLTP concentration, 15,16 but the significance of the PLTP concentration in human diseases is incompletely understood. 5,17 It is, therefore, important to evaluate whether an elevated concentration of serum PLTP is associated with an increased or decreased risk of cardiovascular diseases.…”

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confidence: 99%

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Serum Phospholipid Transfer Protein Mass as a Possible Protective Factor for Coronary Heart Diseases

Yatsuya

Koji

Hashimoto

et al. 2004

Circ J

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n inverse relationship between high-density lipoprotein (HDL) cholesterol and cardiovascular diseases has been demonstrated in epidemiologic studies, 1,2 and is often explained by the capacity of HDL to transport cholesterol from peripheral tissues to the liver, known as reverse cholesterol transport. 3 In this process, pre--HDL, a quantitatively minor subfraction of HDL, is thought to play a critical role because it acts as an efficient acceptor in the cholesterol efflux process from the plasma membrane of peripheral cells. 3,4 Phospholipid transfer protein (PLTP) is capable of generating pre--HDL by inducing HDL conversion, a process that remodels a homogeneous HDL fraction into populations of large and small HDL particles. [5][6][7][8] The transfer of phospholipids to immature HDL in the process of HDL maturation is also essential in maintaining reverse cholesterol transport. 5,9,10 In addition, PLTP has other roles, such as the transfer oftocopherol to cell membrane for the maintenance of endothelial function, or the transfer of lipopolysaccharide to Circulation Journal Vol.68, January 2004 lipoproteins, which leads to neutralization of its potent inflammatory function. 5 Altogether, PLTP can be considered to play an important role in the prevention of atherosclerosis, and thus it has recently attracted much attention.Previous studies regarding PLTP examined its phospholipid transfer activity in patho-physiologic states in human or experimental models. 11-14 Sandwich enzyme-linked immunosorbent assay with 2 monoclonal antibodies to human PLTP has been recently introduced to assay PLTP concentration, 15,16 but the significance of the PLTP concentration in human diseases is incompletely understood. 5,17 It is, therefore, important to evaluate whether an elevated concentration of serum PLTP is associated with an increased or decreased risk of cardiovascular diseases. We examined serum PLTP in relation to newly diagnosed cardiovascular diseases in a middle-aged worksite-based cohort of men in Japan. We also examined the association of serum PLTP concentration with other cardiovascular risk factors. Methods SubjectsThe present analysis is based on a cohort of male workers in a worksite in Aichi prefecture, central Japan. 18,19 Its aim was to determine factors associated with the development of cardiovascular diseases. The study began in 1997, when 2,896 male employees of a manufacturing company, aged 34-59 years, were recruited as potential participants. A self-administered questionnaire was used to assess the

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Quantification of human plasma phospholipid transfer protein (PLTP): relationship between PLTP mass and phospholipid transfer activity

Cited by 65 publications

References 41 publications

Plasma Phospholipid Transfer Protein Activity Is Decreased in Type 2 Diabetes During Treatment With Atorvastatin

Plasma Phospholipid Transfer Protein Activity Is Decreased in Type 2 Diabetes During Treatment With Atorvastatin

Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion

Serum Phospholipid Transfer Protein Mass as a Possible Protective Factor for Coronary Heart Diseases

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