Malondialdehyde/Acetaldehyde Adduct (MAA) is the Dominant Epitope Following MDA Modification of Proteins in Atherosclerosis

• Published in: Free radical biology & medicine Vol. 49; no. 10; pp. 1480 - 1486
• Main Authors: Duryee, Michael J., Klassen, Lynell W., Schaffert, Courtney S., Tuma, Dean J., Hunter, Carlos D., Garvin, Robert P., Anderson, Daniel R., Thiele, Geoffrey M.
• Format: Journal Article
• Language: English
• Published: 06.08.2010
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2010.08.001

Antibodies to malondialdehyde (MDA) modified macromolecules (adducts) have been detected in the serum of patients with atherosclerosis and correlate with the progression of this disease. However, the epitope and its formation have not been characterized. Studies have shown that excess MDA can be degraded to acetaldehyde which combines with proteins to from a stable dihydropyridine adduct. To investigate, mice were immunized with (MDA) adducts in the absence of adjuvant and showed an increase in antibodies to MDA adducts and the carrier protein as the concentration of MDA was increased. In fact, a number of the commercially available antibodies to MDA modified proteins were able to be inhibited by a chemical analogue hexyl-MAA. Also, MDA/MAA adducts were detected in the serum and aortic tissue of JCR diabetic/atherosclerotic rats. These studies determined that commercially available antibodies to MDA were shown to predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and aortic tissue. Therefore, the immune response to MDA modified proteins is most likely to the dihydropyridine structure (predominant epitope in MAA), and suggests that MAA adducts may be playing a role in the development and/or progression of atherosclerosis.