Lipid Transfer Protein Activities in Type 1 Diabetic Patients Without Renal Failure and Nondiabetic Control Subjects and Their Association With Coronary Artery Calcification

Colhoun, Helen M.; Scheek, L.M.; Rubens, Michael B.; Gent, Teus van; Underwood, S. Richard; Fuller, John; Tol, Arie van

doi:10.2337/diabetes.50.3.652

Cited by 58 publications

(47 citation statements)

References 57 publications

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“…Importantly, no alterations in the ability of plasma to promote cellular cholesterol efflux were seen after simvastatin treatment, neither with Fu5AH cells nor with human fibroblasts. Plasma PLTP activity is elevated in type 1 diabetes [13,14] and this increase in PLTP activity is associated with the presence of more large HDL, less small HDL and more plasma apo A-I and apo A-II [13,14]. Our findings with respect to plasma PLTP activity and plasma apo A-I correspond to these studies.…”

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 82%

“…Plasma CETP activity levels were determined after precipitation of endogenous VLDL+LDL with sodium phosphotungstate/MgCl 2 [28]. The isotope assay measures the transfer of radioactive cholesteryl ester between excess exogenous [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C-oleate]-cholesteryl-ester-labelled LDL and an excess of pooled normal HDL, while LCAT is inhibited with dithiobis-2-nitrobenzoic acid. Plasma CETP activity was calculated as the bidirectional transfer between labelled LDL and HDL [29], and reflects the amount of active CETP in plasma.…”

Section: Methodsmentioning

confidence: 99%

“…HDL cholesterol and plasma apo A-I levels are similar, or even higher, in adequately controlled uncomplicated type 1 diabetes [13][14][15]. Plasma PLTP activity is elevated in type 1 diabetic patients [13,14]. Considering the first step in RCT, some studies suggest that in-vitro glycation of HDL impairs its ability to promote cholesterol efflux out of human skin fibroblasts [16], but there are no data with respect to pre-β HDL in type 1 diabetes mellitus.…”

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confidence: 99%

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Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

et al. 2005

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Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 82%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

et al. 2005

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“…However, the available data show high PLTP activity levels in conditions that have been associated with an increased risk of coronary artery disease, i.e. diabetes type 1 and 2, and obesity (12,42,43). Together with mouse data described here, this implies that high PLTP activity is a potential risk factor for coronary artery disease in humans.…”

Section: Discussionmentioning

confidence: 65%

Increased Risk of Atherosclerosis by Elevated Plasma Levels of Phospholipid Transfer Protein

Haperen¹,

Tol²,

Gent³

et al. 2002

Journal of Biological Chemistry

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120

122

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Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (<1.5-fold). The mice were given a high fat, high cholesterol diet, which resulted in hypercholesterolemia in all animals. HDL concentrations were dramatically reduced in PLTP-overexpressing animals when compared with LDL receptor controls, whereas VLDL ؉ LDL cholesterol levels were identical. Susceptibility to atherosclerosis was increased in a PLTP doseresponsive manner. We conclude that PLTP increases susceptibility to atherosclerosis by lowering HDL concentrations, and therefore we suggest that an increase in PLTP is a novel, long term risk factor for atherosclerosis in humans. High density lipoproteins (HDL)1 are believed to be protective against the development of atherosclerosis because they mediate reverse cholesterol transport, i.e. the transfer of cholesterol from peripheral tissues to the liver (1, 2). However, our understanding of the molecular details and key regulatory proteins involved is incomplete (3-5). One effector of this process is the ATP-binding cassette ABCA1, which is functionally deficient in Tangier disease (reviewed in Ref. 6). The high incidence of coronary artery disease in Tangier patients suggests an essential, protective role of HDL-mediated reverse cholesterol transport in the development of atherosclerosis (7).However, recent results suggest that the contribution of ABCA1 to overall reverse cholesterol transport and its role in atherogenesis are primarily related to its function in macrophages (8 -10). Therefore, other potential key proteins in reverse cholesterol transport are of interest, including PLTP (11-13).Previously, we generated transgenic mice overexpressing human PLTP and showed that plasma from these animals is more effective in preventing accumulation of cholesterol by cultured macrophages (14). We and others therefore suggested an antiatherogenic effect for PLTP (14 -16). On the other hand, overexpression of PLTP results in a decrease of plasma HDL levels (14, 17, 18), which could be an atherogenic effect. Thus, it is unclear whether the net effect of high PLTP activity levels would be atherogenic or anti-atherogenic. The complete absence of PLTP activity in PLTP knockout mice inhibits HDL maturation, which results in reduced levels of plasma HDL caused by accelerated decay (19,20). Still, PLTP knockout mice showed decreased atherosclerosis (21). This could be partly explained by the discovery of a novel, intracellular function of PLTP in hepatocytes; it was found that PLTP def...

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Human Plasma Phospholipid Transfer Protein (PLTP) – Structural and Functional Features

Siggins¹,

Rye²,

Olkkonen³

et al. 2007

High‐Density Lipoproteins

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Lipid Transfer Protein Activities in Type 1 Diabetic Patients Without Renal Failure and Nondiabetic Control Subjects and Their Association With Coronary Artery Calcification

Cited by 58 publications

References 57 publications

Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type 1 diabetic patients is enhanced, and is unaffected by simvastatin treatment

Increased Risk of Atherosclerosis by Elevated Plasma Levels of Phospholipid Transfer Protein

Human Plasma Phospholipid Transfer Protein (PLTP) – Structural and Functional Features

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