Publications (2)6.28 Total impact
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Article: Type 2 diabetes mellitus is associated with differential effects on plasma cholesteryl ester transfer protein and phospholipid transfer protein activities and concentrations.
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ABSTRACT: Human plasma contains two lipid transfer proteins, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which are crucial in reverse cholesterol transport. Plasma CETP and PLTP activity levels and concentrations in 16 type 2 diabetic patients and 16 matched healthy subjects were determined, and these data were correlated to clinical variables, including insulin sensitivity and lipid levels. Plasma triglycerides were higher (p<0.02) and high-density lipoprotein (HDL) cholesterol (p<0.02) was lower in diabetic patients. Plasma CETP activity and concentrations were not significantly different between diabetic and healthy subjects, but CETP specific activity was lower in diabetic patients (p<0.001). Multiple regression analysis showed that plasma CETP activity was positively related to CETP concentration (p=0.0001) and negatively to the diabetic state (p<0.002) or to HbA1c (p<0.02). PLTP activity (p<0.05) and specific activity were higher (p<0.05), whereas there was no difference in PLTP concentration between the two groups. There was no significant bivariate correlation between PLTP concentration and activity, in either healthy or diabetic subjects. Multiple regression analysis did disclose positive relationships of PLTP activity with PLTP concentration (p=0.0001), plasma triglycerides (p=0.0001) and waist/hip ratio (p=0.0001), but not with the diabetic state or HbA1c. Neither CETP nor PLTP activity was independently associated with insulin sensitivity. Specific CETP activity is decreased in type 2 diabetes mellitus. In contrast, specific PLTP activity is higher in diabetes, as a result of the association of plasma PLTP activity with plasma triglycerides and obesity. Measurement of both plasma lipid transfer protein activity and mass levels may thus provide extra information in diabetes mellitus.Scandinavian Journal of Clinical and Laboratory Investigation 01/2004; 64(3):205-15. · 1.38 Impact Factor -
Article: Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins.
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ABSTRACT: High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.Biochemical Journal 01/2002; 360(Pt 2):379-85. · 4.90 Impact Factor
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Institutions
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2004
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Erasmus Universiteit Rotterdam
- Department of Biochemistry
Rotterdam, South Holland, Netherlands
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