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Antiphospholipid antibodies and atherosclerosis
E Matsuura1, K Kobayashi, T Yasuda
1Department of Cell Chemistry, Institute of Cellular and Molecular Biology, Okayama University Medical School, Japan.
Lupus
|November 14, 1998
Summary
Beta2-Glycoprotein I (beta2-GPI) and anticardiolipin antibodies (aCL) target oxidized LDL, but not MDA-modified LDL. Immune responses to beta2-GPI may promote atherosclerosis.
Area of Science:
- Immunology
- Biochemistry
- Cardiovascular Research
Background:
- Beta2-Glycoprotein I (beta2-GPI) is a key antigen for anticardiolipin antibodies (aCL) in antiphospholipid syndrome.
- The antigenic epitopes of beta2-GPI are typically cryptic, becoming exposed upon interaction with negatively charged phospholipids or specific surfaces.
- Antiphospholipid syndrome is associated with an increased risk of thrombosis and other complications.
Purpose of the Study:
- To investigate the interaction of beta2-GPI and aCL with modified low-density lipoproteins (LDL).
- To determine the nature of the LDL modifications that trigger binding by beta2-GPI and aCL.
- To explore the potential role of immune responses against beta2-GPI in atherogenesis.
Main Methods:
- Oxidation of LDL using CuSO4 to generate oxidized LDL (oxLDL).
- Modification of LDL with malondialdehyde (MDA).
- Assessing beta2-GPI and aCL binding to native, oxLDL, and MDA-modified LDL.
- Quantifying LDL oxidation using thiobarbituric acid-reactive substances (TBARS).
- Investigating the effect of anti-beta2-GPI immune responses on macrophage uptake of oxLDL in vitro.
Main Results:
- Beta2-GPI and aCL specifically targeted CuSO4-oxidized LDL (oxLDL).
- Malondialdehyde (MDA)-modified LDL were not recognized by beta2-GPI or aCL.
- Beta2-GPI binding to LDL increased significantly upon CuSO4-induced oxidation.
- LDL oxidation was associated with increased TBARS and apolipoprotein denaturation.
- Intermediate oxidative derivatives of LDL, not MDA, were identified as ligands for beta2-GPI.
- Immune responses against beta2-GPI induced an atherogenic effect in oxLDL uptake by macrophages.
Conclusions:
- Beta2-GPI and aCL recognize specific oxidative modifications in LDL, particularly those induced by CuSO4, but not MDA modification.
- The interaction of beta2-GPI with oxLDL involves intermediate oxidative derivatives.
- Immune responses directed against beta2-GPI may contribute to the development of atherosclerosis through enhanced oxLDL uptake by macrophages.