Plasma lipoproteins from patients with poorly controlled diabetes mellitus and "in vitro" glycation of lipoproteins enhance the transfer rate of cholesteryl ester from HDL to apo-B-containing lipoproteins.
Alterations in the reverse cholesterol transport system have been described in diabetic mellitus patients in several but not all studies. Furthermore, recently published investigations suggest that a faster "in vitro" transfer rate of cholesteryl ester from high density lipoproteins to apoB-containing lipoproteins could be solely ascribed to variation of the plasma lipoprotein composition and concentration in the diabetic state. The present study analysed the influence of lipoprotein glycation on the cholesteryl ester transfer protein-mediated transfer of esterified cholesterol from high density lipoprotein and its subfractions to lighter density lipoproteins. For this purpose two sets of "in vitro" experiments were carried out utilizing:1) plasma lipoproteins drawn from diabetic and from normal subjects and; 2) normal lipoproteins or partially purified cholesteryl ester transfer protein submitted to "in vitro" glycation. The transfer rate of 14C-cholesteryl ester labelled HDL subfractions to low or very low density lipoproteins was measured in all experiments. After incubations with plasma d > 1.21 g/ml or with purified cholesteryl ester transfer protein, apoB-containing lipoproteins were precipitated with a dextran sulfate/MgCl2 solution. The "in vitro" glycation of the partially purified cholesteryl ester transfer protein, markedly impaired its activity. However, greater transfer rates were observed when lipoproteins from diabetic individuals or the "in vitro" glycated lipoproteins were utilized. This effect was attributed to glycation of the protein component of HDL. In conclusion, lipoprotein glycation elicits an enrichment of the apoB-containing lipoproteins with cholesteryl ester that is likely related to the premature atherosclerosis in patients with poorly controlled diabetes.
Passarelli
M
M
Lipids Laboratory, University of São Paulo Medical School, Brazil.
Catanozi
S
S
Nakandakare
E R
ER
Rocha
J C
JC
Morton
R E
RE
Shimabukuro
A F
AF
Quintão
E C
EC
D001055:Apolipoproteins B / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D015243:Cholesterol, VLDL / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood* / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D004951:Esterification; D006023:Glycoproteins; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism*
D001055:Apolipoproteins B; C506642:CETP protein, human; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006023:Glycoproteins; D008074:Lipoproteins