Autoantibodies against aldehyde-modified collagen type IV are associated with risk of development of myocardial infarction

Research output: Contribution to journalArticle

Abstract

Background: Oxidation of LDL particles entrapped in the extracellular matrix of the arterial wall is a key factor in the development of atherosclerosis. Lipid oxidation products, such as malondialdehyde (MDA), react with surrounding extracellular matrix proteins and cause modifications that are recognized by the immune system. MDA modification of collagen type IV is increased in carotid lesions from symptomatic patients and correlates with autoantibodies against MDA-modified collagen type IV in plasma. Objective: The aim of this study was to determine whether autoantibodies against MDA-modified collagen type IV predict risk of development of myocardial infarction (MI). Methods: Plasma levels of MDA-modified collagen type IV IgM and IgG antibodies were analysed by enzyme-linked immunosorbent assay in 385 subjects with incident MI during 13 years of follow-up and 410 age- and sex-matched controls in the Malmö Diet and Cancer study. Results: MDA-modified collagen type IV IgG levels were higher in cases with incident MI than in controls. Subjects in the highest tertile of MDA-modified collagen type IV IgG had an increased risk of MI (hazard ratio 1.56, 95% confidence interval 1.22-2.00, P for trend 0.0004). This association remained significant after adjusting for factors included in the Framingham risk score and diabetes. High levels of MDA-collagen type IV IgG were associated with increased carotid intima-media thickness and elevated plasma levels of matrix metalloproteinase 10 and 12. Conclusions: Immune responses against MDA-modified collagen type IV are associated with more severe carotid disease and increased risk of MI. These immune responses may reflect LDL oxidation in the artery wall, but could also affect the atherosclerotic disease process.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • Autoantibodies, Malondialdehyde, Myocardial infarction
Original languageEnglish
Pages (from-to)496-507
JournalJournal of Internal Medicine
Volume282
Issue number6
Early online date2017
Publication statusPublished - 2017 Dec
Publication categoryResearch
Peer-reviewedYes

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