Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

Riemens, Stephen; Tol, Arie van; Sluiter, Wim J.; Dullaart, Robin P. F.

doi:10.1016/s0021-9150(98)00111-7

Cited by 119 publications

(138 citation statements)

References 59 publications

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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: Discussionsupporting

confidence: 62%

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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116

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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Section: Discussionsupporting

confidence: 62%

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

Haperen¹,

Tol²,

Gent³

et al. 2002

Journal of Biological Chemistry

Self Cite

116

122

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“…The finding of increased phospholipid transfer in diabetic patients, suggesting higher PLTP activity, is consistent with some reports in the literature 13,14 . Earlier studies have also shown an increase in plasma cholesteryl ester transfer 15,16 The relationship between microalbuminuria and dyslipidemia in diabetic patients has been well explored.…”

Section: Discussionsupporting

confidence: 92%

Transferências lipídicas para HDL em diabéticos tipo 2: associações com microalbuminúria, estatina e insulina

Feitosa-Filho¹,

Seydell²,

Feitosa³

et al. 2009

Arq. Bras. Cardiol.

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“…As a result, VLDL competes with the alimentary lipoproteins for the available lipoprotein lipase (LPL) activity needed to produce remnant particles destined for hepatic uptake along with intermediate-density lipoprotein, the precursor of LDL [7]. Along with prolonged lipaemia, abnormal lipid exchange mediated by specific transfer proteins leads to formation of triglyceride-rich LDL and HDL [8]. These are substrates for hepatic lipase, the activity of which is increased in insulin resistance and generates atherogenic small dense LDL and HDL species that, together with prolonged postprandial lipaemia itself, have been shown to be cardiovascular disease risk factors [9,10].…”

Section: Introductionmentioning

confidence: 99%

The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients

et al. 2006

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Aims/hypothesis: Insulin resistance is thought to be central to the pathogenesis of diabetic dyslipidaemia. We hypothesised that improving insulin sensitivity would improve fasting and postprandial triglyceride metabolism in patients with type 2 diabetes. To this aim we studied fasting and postprandial lipaemia in type 2 diabetic patients before and after sensitisation to insulin with pioglitazone, compared with that observed in patients on an insulinproviding regime. Methods: In a double-blind placebo-controlled protocol, 22 patients with type 2 diabetes were randomly allocated to receive either pioglitazone (45 mg/day) or glibenclamide (5 mg/day), for a 20-week period. Fasting and postprandial lipid metabolism were investigated at baseline and at the end of the treatment period. A group of non-diabetic subjects was also studied. Results: Compared with glibenclamide treatment, pioglitazone treatment decreased fasting triglyceride, glucose and insulin levels and the homeostasis model assessment score of insulin resistance. Decreased fasting triglyceride after pioglitazone treatment was due to reduced VLDL triglyceride, particularly VLDL-2. Lipoprotein lipase activity was unchanged by pioglitazone treatment but hepatic lipase showed a significant decrease. Pioglitazone treatment lowered total postprandial triglyceride, as well as chylomicron-and chylomicron-remnant retinyl palmitate levels to normal. Glucose disposal improved but remained abnormal. Conclusions/interpretation: Insulin sensitisation with pioglitazone has major effects in restoring postprandial lipaemia to normal, while also correcting fasting hypertriglyceridaemia; both factors may have consequences for atherogenic risk in diabetes.

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Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein

Cited by 119 publications

References 59 publications

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

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

Transferências lipídicas para HDL em diabéticos tipo 2: associações com microalbuminúria, estatina e insulina

The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients

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