Glycation of plasma low density lipoproteins increases interaction with arterial proteoglycans.
The increased susceptibility to atherosclerosis of diabetic individuals, may result from diabetes-associated modification in plasma low density lipoproteins (LDL) which enhance their interaction with arterial extracellular matrix proteoglycans. Using a nonhuman primate model for human diabetes, studies were conducted to examine diabetes-induced changes in LDL. Plasma LDL were isolated from control (n = 4) and streptozotocin-induced diabetic (n = 3) cynomolgus macaques by differential ultracentrifugation. An in vitro binding assay was used to measure LDL interaction with arterial proteoglycans. Significantly more diabetic LDL bound to proteoglycans than control LDL (12.9+/-0.7 microg LDL cholesterol/microg proteoglycan versus 8.9+/-0.5 microg LDL cholesterol/microg proteoglycan (mean +/- S.E.M.), P < 0.005). Glycation of LDL, determined by fructosamine content, was significantly enhanced in diabetic versus control animals (37+/-3.1 versus 20+/-1.5 micromol/l (mean +/- S.E.M.) P < 0.005). The correlation coefficient between fructosamine content of LDL and its binding to arterial proteoglycans was 0.95. No LDL compositional variables other than glycation correlated with proteoglycan binding. Removal of the glycated portion of LDL from diabetic animals returned LDL proteoglycan binding to normal. These data demonstrate that the diabetes induced glycation of LDL increases its proteoglycan binding properties: thus, a critical mechanism in atherosclerosis, enhanced LDL interaction with arterial proteoglycans, may be accelerated by the diabetic state.
Edwards
I J
IJ
Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1047, USA. iedwards@wfubmc.edu
Wagner
J D
JD
Litwak
K N
KN
Rudel
L L
LL
Cefalu
W T
WT
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000503:physiopathology*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood*; D008252:Macaca fascicularis; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D012016:Reference Values; D000093844:Glycated Proteins
D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; D011509:Proteoglycans; C031797:glycated lipoproteins, LDL; D000093844:Glycated Proteins