Autoantibodies against oxidized low-density lipoprotein (ox-LDL) and LDL oxidation status

Abstract

Oxidized low-density lipoproteins (ox-LDLs) and their autoantibodies (OLAB) are involved in the development of atherosclerosis in animal models, but their role in humans is still not clear. For this reason we studied 54 patients with beta-thalassemia major (TM), as a model of chronically low circulating LDLs with a high level of oxidation; 44 patients with primary hypercholesterolemia, as model of chronically high circulating LDLs; 24 type 2 diabetic mellitus patients (T2DM) before and after 3 months of atorvastatin treatment (20 mg/day), as a model of acute changes in circulating LDLs; and 41 normolipidemic subjects as a control group. ox-LDLs were measured by the determination of baseline diene concentration in the plasma LDL lipidic fraction after 12 hours fasting and were expressed as the amount of conjugated dienes/ liter (BDC/I) or BDC/LDL-cholesterol (LDL-C), which indicate respectively LDL oxidation degree and status. OLAB were determined using an enzyme immunoassay and related to LDL oxidation degree (BDC/I). In TM, BDC/I was lower, while BDC/LDL-C was significantly higher, compared to both hypercholesterolemia and normolipidemic subjects. Patients with hypercholesterolemia had higher BDC/I, but lower BDC/LDL-C and OLAB/BDC-I, than normolipidemic subjects. In T2DM patients at diet, BDC/LDL-C and OLAB/BDC-I were lower than in normolipidemic subjects. After 3 months of atorvastatin treatment, BDC/ LDL-C and OLAB/BDC-I ratios increased. When all patients were evaluated together, a significant inverse correlation was evident between OLAB and either LDL or BDC/I. Our findings suggest that a relationship between OLAB titer and oxidation indices (BDC/I and BDC/LDL-C) does exist and we may speculate that an increase in OLAB/BDC-I ratio might be protective against the risk of atherosclerosis.

Subclinical Atherosclerosis In Young β-thalassemia Major Patients

“…Other studies have found that circulating LDL of b-TM patients are more susceptible to oxidation not only due to iron overload but also due to decreased HDL levels in those patients (20). Moreover, Brizzi et al (19) reported that in b-TM patients, since iron overload depletes the antioxidant and HDL-C is lower than normal, then LDL composition is mainly influenced by the TG level.…”

“…Although serum LDL may be normal or high in thalassemic patients, it is subjected to peroxidative stress due to iron overload secondary to blood transfusions that could represent an event leading to atherosclerogenesis (19). Moreover, steatosis and chronic viral hepatitis induce hepatic acutephase response, which is associated with an enhanced LDL secretion (20). An important role of unpaired Hb chains and red blood cell hemolysis products are also under consideration since it has been observed that the interaction between Hb a chain and LDL leads to the oxidative modification of LDL (21).…”

Using Oxidized Low-Density Lipoprotein Autoantibodies to Predict Restenosis after Balloon Angioplasty in Patients with Acute Myocardial Infarction

“…Additionally, OLAB levels appear to be negatively correlated with indices of oxidative stress [23] and negatively associated with the severity and extent of stenotic coronary lesions [24]. Therefore, OLAB may protect against atherosclerosis by attenuating oxidative stress.…”

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

“…In a recent study, a significant inverse correlation between the presence of anti-oxLDL autoantibodies and the degree of LDL or LDL oxidation was demonstrated (45), suggesting that the increase in anti-oxLDL antibodies and the extent of the LDL oxidation ratio is protective against atherosclerosis. The findings are indeed conflicting, since some anti-oxLDL autoantibodies seem to be protective, whereas many others are found to be correlated with the extent of atherosclerosis; thus, antioxLDL can be characterized as either predictive or pathogenic.…”