Immunological response to oxidized LDL occurs in association with oxidative DNA damage independently of serum LDL concentrations in dyslipidemic patients.
Oxidative modification of LDL induces immunogenic epitopes in the LDL molecule, and the presence of antibodies against oxidized LDL (anti-Ox-LDL) has been demonstrated in human sera. However, little is known about the clinical significance of anti-Ox-LDL. To elucidate a clinical relationship between the immunological response to oxidized LDL and cellular oxidative stress, we measured serum titers of anti-Ox-LDL in 45 unselected patients with hypercholesterolemia and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), considered a biomarker of the oxidative damage to DNA. The anti-Ox-LDL titer was not correlated with the serum LDL-C concentration, but was correlated with the 8-OHdG concentration (r = 0.300, P < 0.05) in a simple linear regression. Multiple regression analysis indicated that 8-OHdG was independently correlated with anti-Ox-LDL (r = 0.429, P < 0.05), but no other variables, including LDL-C concentrations and smoking habit, were correlated with anti-Ox-LDL. In 16 subgroup patients, the concentrations of TC, TG and LDL-C decreased and the HDL-C concentration increased after cholesterol-lowering therapy with fluvastatin. In addition, both the anti-Ox LDL titer (14.0 +/- 9.5 to 11.4 +/- 6.6 AcU/ml, P < 0.05) and the 8-OHdG concentration (1.19 +/- 0.41 to 0.85 +/- 0.43 ng/ml, P < 0.05) also decreased after fluvastatin therapy. The immunological response to LDL oxidation on vascular wall tissues or cells appear to occur in association with oxidative DNA damage. The measurement of anti-Ox-LDL may be a useful indicator for lipid-lowering therapy.
Inoue
T
T
Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minamikoshigaya, Saitama 343-8555, Koshigaya City, Japan. inouet@dokkyomed.ac.jp
Inoue
K
K
Maeda
H
H
Takayanagi
K
K
Morooka
S
S
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D004249:DNA Damage; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D000077340:Fluvastatin; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D007211:Indoles / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000276:immunology*; D018384:Oxidative Stress
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D000077340:Fluvastatin