This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seccia, M. Articles by Bellomo, G. Search for Related Content PubMed PubMed Citation Articles by Seccia, M. Articles by Bellomo, G. Pubmed/NCBI databases Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:134-140.)
© 1997 American Heart Association, Inc.

Articles

Circulating Autoantibodies Recognizing Peroxidase-Oxidized Low Density Lipoprotein

Evidence for New Antigenic Epitopes Formed In Vivo Independently From Lipid Peroxidation

Milfred Seccia; Emanuele Albano; Elena Maggi; Giorgio Bellomo

the Department of Medical Sciences, University of Torino, Novara (M.S., E.A., G.B.) and Department of Internal Medicine and Medical Therapeutics, University of Pavia, Italy (E.M.).

Correspondence to Prof Giorgio Bellomo, MD, Department of Medical Sciences, University of Torino, Via Solaroli 17, I-28100 Novara, Italy.

Oxidatively modified LDLs are antigenic and elicit the generation of autoantibodies often detected in plasma and within plaques of atherosclerotic patients. Although Cu²⁺-oxidized LDL and malondialdehyde (MDA)–modified LDL are usually used as antigens in immunoassays, other, still unrecognized epitopes may be formed in vivo during LDL oxidation and may induce antibody production. Antibodies recognizing LDL oxidatively modified by Cu²⁺, 2,2'-azobis-(2-amidino propane) hydrochloride (AAPH), and the combination of horseradish peroxidase and H₂O₂ (HRP) were detected in serum of a group of 90 unselected patients. HRP-oxidized LDL was the antigen that revealed the highest IgG titers, although the extent of LDL oxidation (evaluated as conjugated diene formation, loss of tryptophan fluorescence, production of fluorescent aldehydic adducts, and change in electrophoretic mobility) was comparable to that obtained with Cu²⁺ and AAPH. There was a highly statistically significant correlation between the IgG titers detected using Cu²⁺- and AAPH-oxidized LDLs as antigens, but no correlation was found between the IgG titers revealed by HRP and Cu²⁺ or AAPH. In addition, the antibody titers against MDA-modified LDL exhibited a significant correlation with those against Cu²⁺- or AAPH-oxidized LDL but did not correlate with those against HRP-oxidized LDL. Finally, immunocompetition experiments revealed that IgG recognizing HRP-oxidized LDL did not cross-react with Cu²⁺-oxidized LDL and vice versa. The possibility that lipid peroxidation–independent modifications could play a role in HRP-induced formation of antigenic epitopes in LDL was supported by two lines of evidence. First, in probucol-enriched LDL, despite the complete inhibition of lipid peroxidation, HRP, but not Cu²⁺ and AAPH, was still able to generate epitopes that were recognized by the same sera reacting with HRP-oxidized native (not probucol-enriched) LDL. In addition, the presence of autoantibodies against Cu²⁺- and AAPH-oxidized LDLs was negatively correlated with serum -tocopherol concentration, whereas the titers against HRP-oxidized LDL did not exhibit any statistically relevant correlation with -tocopherol levels. Together, these findings indicate that peroxidase(s)-dependent mechanisms can trigger peculiar lipid peroxidation–independent modifications of LDL in vivo.

Key Words: LDL • oxidation • peroxidases • autoantibodies • atherosclerosis

This article has been cited by other articles:

				B. de Geest and D. Collen Antibodies against oxidized LDL for non-invasive diagnosis of atherosclerotic vascular disease Eur. Heart J., September 1, 2001; 22(17): 1517 - 1518. [PDF]

				A. T. Erkkila, O. Narvanen, S. Lehto, M. I. J. Uusitupa, and S. Yla-Herttuala Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 204 - 209. [Abstract] [Full Text] [PDF]

				S. Parthasarathy, N. Santanam, S. Ramachandran, and O. Meilhac Oxidants and antioxidants in atherogenesis: an appraisal J. Lipid Res., December 1, 1999; 40(12): 2143 - 2157. [Abstract] [Full Text] [PDF]

				P. M. Morganelli, D. S. Groveman, and J. R. Pfeiffer Evidence That Human Fc{gamma} Receptor IIA (CD32) Subtypes Are Not Receptors for Oxidized LDL Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3248 - 3254. [Abstract] [Full Text]

				M. Seccia, E. Albano, and G. Bellomo Suitability of chemical in vitro models to investigate LDL oxidation: study with different initiating conditions in native and {alpha}-tocopherol-supplemented LDL Clin. Chem., August 1, 1997; 43(8): 1436 - 1441. [Abstract] [Full Text] [PDF]