Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis

Michael J. Duryee, Lynell Warren Klassen, Courtney S. Schaffert, Dean J. Tuma, Carlos D. Hunter, Robert P. Garvin, Daniel R Anderson, Geoffrey Milton Thiele

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 predominantly react with the MAA adduct and are present in the JCR model of atherosclerosis in both the serum and the aortic tissue. Therefore, the immune response to MDA-modified proteins is most probably to the dihydropyridine structure (predominant epitope in MAA), which suggests that MAA adducts may play a role in the development and/or progression of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1480-1486
Number of pages7
JournalFree Radical Biology and Medicine
Volume49
Issue number10
DOIs
StatePublished - Nov 30 2010

Fingerprint

Acetaldehyde
Malondialdehyde
Epitopes
Atherosclerosis
Proteins
Antibodies
Serum
Tissue
Macromolecules
Disease Progression
Rats
Carrier Proteins

Keywords

  • Acetaldehyde
  • Atherosclerosis
  • Autoantibodies
  • JCR rats
  • Lipid peroxidation
  • Malondialdehyde
  • Modified proteins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis. / Duryee, Michael J.; Klassen, Lynell Warren; Schaffert, Courtney S.; Tuma, Dean J.; Hunter, Carlos D.; Garvin, Robert P.; Anderson, Daniel R; Thiele, Geoffrey Milton.

In: Free Radical Biology and Medicine, Vol. 49, No. 10, 30.11.2010, p. 1480-1486.

Research output: Contribution to journalArticle

Duryee, Michael J. ; Klassen, Lynell Warren ; Schaffert, Courtney S. ; Tuma, Dean J. ; Hunter, Carlos D. ; Garvin, Robert P. ; Anderson, Daniel R ; Thiele, Geoffrey Milton. / Malondialdehyde-acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 10. pp. 1480-1486.
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