Glucose-modified low density lipoprotein enhances human monocyte chemotaxis.
In diabetes mellitus the progression of atherosclerosis is accelerated. The interaction of glucose with atherogenic lipoproteins may be relevant to the mechanisms responsible for this vascular damage. The aim of this study was to examine the effect of glucose-modified low density lipoprotein (LDL) on human monocyte chemotaxis and to investigate the roles of oxidation and glycation in the generation of chemotactic LDL. Cu(II)-mediated LDL oxidation was potentiated by glucose in a dose-dependent manner and increased its chemotactic activity. Incubation with glucose alone, under conditions where very little oxidation was observed, also increased the chemotactic property of LDL. Neither diethylenetriamine pentaacetic acid (DETAPAC) nor aminoguanidine, which both inhibited LDL oxidation, completely inhibited the chemotactic activity of glycated oxidised LDL. The results suggest that both oxidation and glycation contribute to increased chemotactic activity.
University of Cambridge, Department of Pathology, Cambridge, UK.
S A
SA
Millican
D
D
Schultz
M
M
Bagga
P J
PJ
Coussons
K
K
Müller
J V
JV
Hunt
D002614:Chelating Agents / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D004369:Pentetic Acid / Q000494:pharmacology
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D008077:Lipoproteins, LDL; D004369:Pentetic Acid; D005947:Glucose; C004479:pimagedine