Autoantibodies against oxidatively modified low-density lipoproteins in NIDDM.
Diabetes is an independent risk factor in the development of atherosclerosis, although the pathophysiological processes underlying this association are poorly understood. The oxidation of low-density lipoprotein (LDL) is considered a key event in the development and progression of atherosclerosis because it generates molecular epitopes that are more atherogenic than parent LDL. A total of 138 patients suffering from non-insulin-dependent diabetes mellitus (NIDDM) and 80 matched control subjects were investigated. LDL oxidation was evaluated as the presence of autoantibodies against oxidatively modified LDL, since they mirror the in vivo occurrence of oxidative processes. NIDDM patients had an antibody ratio (calculated as the ratio of antibodies against modified versus native LDL) significantly higher than control subjects for Cu(2+)-oxidized LDL (1.88 +/- 0.6 vs. 1.05 +/- 0.3, P < 0.01, for IgG), malondialdehyde-modified LDL (2.54 +/- 0.73 vs. 2.04 +/- 0.11, P < 0.01, for IgG and 3.96 +/- 1.51 vs. 2.90 +/- 0.15, P < 0.01, for IgM), and malondialdehyde-modified human serum albumin (1.79 +/- 0.54 vs. 1.46 +/- 0.1, P < 0.05 for IgG). The possible role played by glycation in sensitizing LDL to oxidation was investigated by measuring autoantibodies against both glycated LDL (glycLDL) and glycoxydated LDL (glycoxLDL). NIDDM patients had an antibody ratio significantly higher than control subjects for anti-glycLDL and anti-glycoxLDL IgG (1.79 +/- 0.38 vs. 1.12 +/- 0.23, P < 0.01 and 2.55 +/- 1.03 vs. 1.39 +/- 0.44, P < 0.01, respectively) but not anti-glycLDL and anti-glycox-LDL IgM.(ABSTRACT TRUNCATED AT 250 WORDS)
Bellomo
G
G
Department of Medical Sciences, 2nd Faculty of Medicine, University of Torino, Novara, Italy.
Maggi
E
E
Poli
M
M
Agosta
F G
FG
Bollati
P
P
Finardi
G
G
D000368:Aged; D001161:Arteriosclerosis / Q000453:epidemiology / Q000209:etiology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012307:Risk Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL