Immunological response to oxidized LDL occurs in association with oxidative DNA damage independently of serum LDL concentrations in dyslipidemic patients

Clin Chim Acta. 2001 Mar;305(1-2):115-21. doi: 10.1016/s0009-8981(00)00426-5.

Abstract

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.

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • DNA Damage*
  • Fatty Acids, Monounsaturated / therapeutic use
  • Fluvastatin
  • Humans
  • Hypercholesterolemia / blood*
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / immunology
  • Indoles / therapeutic use
  • Lipoproteins, LDL / immunology*
  • Oxidative Stress*

Substances

  • Anticholesteremic Agents
  • Fatty Acids, Monounsaturated
  • Indoles
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Fluvastatin