Non-enzymatic glycation of lipoprotein(a) in vitro and in vivo.
Nonenzymatic glycation of lipoprotein may contribute to the premature atherogenesis of patients with diabetes mellitus by diverting lipoprotein catabolism from non-atherogenic to atherogenic pathways. It has been demonstrated that the proportion of apolipoprotein B-100 (apo B-100) in glycated form is significantly higher in diabetic patients than in non-diabetic controls, and equally that plasma lipoprotein(a) Lp(a) levels may be increased in diabetic patients. Consequently, we have evaluated the glycation of Lp(a) in vitro and in vivo, by use of a combination of m-aminophenylboronate affinity chromatography and enzyme-linked immunosorbent assay (ELISA) for apo B-100 and Lp(a). In vitro studies were performed on normolipodemic plasma samples containing elevated concentrations of Lp(a). These studies establish that Lp(a) can be glycated in vitro in the presence of high concentrations of glucose, although to a lesser extent than low density lipoprotein (LDL) (15.8% +/- 4.4% and 30.2% +/- 5.4% (P = 0.0001) after a 48 h incubation at 37 degrees C, respectively). We have also shown that apo B-100 was more glycated than apo(a) in the Lp(a) particle. In vivo studies have shown that the percentage of glycated Lp(a) in diabetic patients was significantly higher than in the control population (2.8% +/- 1.07% versus 2.0% +/- 0.43%, P = 0.017). The level of glycated Lp(a) is also positively correlated with that of HbA1c in diabetic patients (r=0.6, P=0.002). Since our results show that Lp(a) is less susceptible to glycation than LDL, we speculate that glycation of LDL may be more relevant to the cardiovascular risk associated with this particle than with Lp(a).
Doucet
C
C
Institut National de la Santé et de la Recherche Médicale, Hôpital de la Pitié, Paris, France.
Huby
T
T
Ruiz
J
J
Chapman
M J
MJ
Thillet
J
J
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL