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

Vallejo, J. LU ; Dunér, P. LU ; Fredrikson, G. N. LU ; Nilsson, Jan LU and Bengtsson, Eva LU (2017) In Journal of Internal Medicine1989-01-01+01:00 282(6). p.496-507
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoantibodies, Malondialdehyde, Myocardial infarction
in
Journal of Internal Medicine1989-01-01+01:00
volume
282
issue
6
pages
496 - 507
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • scopus:85030246265
  • wos:000415928700003
ISSN
0954-6820
DOI
10.1111/joim.12659
language
English
LU publication?
yes
id
2328f4dc-ba27-4ec4-a9bc-995b987ab41b
date added to LUP
2017-11-03 09:45:46
date last changed
2018-09-16 04:50:59
@article{2328f4dc-ba27-4ec4-a9bc-995b987ab41b,
  abstract     = {<p>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.</p>},
  author       = {Vallejo, J. and Dunér, P. and Fredrikson, G. N. and Nilsson, Jan and Bengtsson, Eva},
  issn         = {0954-6820},
  keyword      = {Autoantibodies,Malondialdehyde,Myocardial infarction},
  language     = {eng},
  number       = {6},
  pages        = {496--507},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine1989-01-01+01:00},
  title        = {Autoantibodies against aldehyde-modified collagen type IV are associated with risk of development of myocardial infarction},
  url          = {http://dx.doi.org/10.1111/joim.12659},
  volume       = {282},
  year         = {2017},
}