The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity.
OBJECTIVE
Chemical and biological characteristics of LDL(-) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control.


METHODS
Total LDL was subfractionated into electropositive LDL(+) and electronegative LDL(-) by anion exchange chromatography and the lipid and protein composition of the two determined.


RESULTS
LDL(-) differed from LDL(+) in that it had higher triglyceride, non-esterified fatty acids, apoE, apoC-III and platelet-activating factor acetylhydrolase (PAF-AH), as well as lower apoB relative content. No evidence of increased oxidation was observed in LDL(-). LDL(-) increased two-fold the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells, suggesting an inflammatory role. Optimisation of glycaemic control after insulin therapy decreased the proportion of LDL(-), but did not modify the composition of LDL subfractions, except for a decrease in PAF-AH activity in LDL(-). The possibility that LDL(-) could be generated by non-enzymatic glycosylation was studied. Fructosamine and glycated LDL content in LDL subfractions from type 1 diabetic patients was greater than in LDL subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. However, no difference was observed between LDL(+) and LDL(-) before and after insulin therapy.


CONCLUSIONS
These results provide evidence that LDL(-) is not produced by glycosylation. Nevertheless, LDL(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. This proatherogenic effect could be related to the high PAF-AH activity in LDL(-).
Sánchez-Quesada
J L
JL
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Benítez
S
S
Pérez
A
A
Wagner
A M
AM
Rigla
M
M
Carreras
G
G
Vila
L
L
Camacho
M
M
Arcelus
R
R
Ordóñez-Llanos
J
J
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D001059:Apoproteins / Q000737:chemistry; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018925:Chemokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000633:toxicity*; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D014157:Transcription Factors
D001059:Apoproteins; D001786:Blood Glucose; D018925:Chemokines; D008055:Lipids; D008077:Lipoproteins, LDL; D014157:Transcription Factors; D008315:Malondialdehyde; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase