The inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients are related to increased platelet-activating factor acetylhydrolase activity

Chemical and biological characteristics of LDL(−) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control.

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

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.

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(−).