Autoantibodies against aldehyde‐modified collagen type <scp>IV</scp> are associated with risk of development of myocardial infarction

Vallejo, Jenifer; Dunér, Pontus; Fredrikson, Gunilla Nordin; Nilsson, Jan; Bengtsson, Eva

doi:10.1111/joim.12659

Cited by 7 publications

(7 citation statements)

References 54 publications

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“…2, process 10) (34), suggesting an atheropromoting effect of MDA-collagen type IV. Besides altering functional properties of collagen type IV, the reaction with MDA generates neoepitopes leading to the generation of autoantibodies, which are detectable in the circulation and display correlation to CVD end points (34,90,147). This, however, is not specific to autoantibodies against MDA-collagen type IV since autoantibodies against MDA-laminin, MDAfibronectin, and MDA-APOB100 also display such correlations (147), indicating that these autoantibodies merely reflect lipoprotein oxidation.…”

Section: Autoantibodiesmentioning

confidence: 99%

A role for collagen type IV in cardiovascular disease?

Steffensen

Rasmussen

2018

American Journal of Physiology-Heart and Circulatory Physiology

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Over the past decade, studies have repeatedly found single-nucleotide polymorphisms located in the collagen ( COL) 4A1 and COL4A2 genes to be associated with cardiovascular disease (CVD), and the 13q34 locus harboring these genes is one of ~160 genome-wide significant risk loci for coronary artery disease. COL4A1 and COL4A2 encode the α- and α-chains of collagen type IV, a major component of basement membranes in various tissues including arteries. Despite the growing body of evidence indicating a role for collagen type IV in CVD, remarkably few studies have aimed to directly investigate such a role. The purpose of this review is to summarize the clinical reports linking 13q34 to coronary artery disease, atherosclerosis, and artery stiffening and to assemble the scattered pieces of evidence from experimental studies based on vascular cells and tissue collectively supporting a role for collagen type IV in atherosclerosis and other macrovascular disease conditions.

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Section: Autoantibodiesmentioning

confidence: 99%

A role for collagen type IV in cardiovascular disease?

Steffensen

Rasmussen

2018

American Journal of Physiology-Heart and Circulatory Physiology

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“…We have recently demonstrated an association between autoantibodies against MDA-modified collagen type IV and risk for development of myocardial infarction 8 . To investigate if immune responses against collagen type IV could contribute to vascular injury affecting the development of atherosclerosis we immunized ApoE −/− mice with native or MDA-collagen type IV using Alum, Freund’s incomplete or Freund’s complete as adjuvants.…”

Section: Resultsmentioning

confidence: 99%

“…The lack of effect on atherosclerosis by immunization with collagen type IV α1α2 peptides suggests that autoantibodies against collagen type IV, previously associated with cardiovascular disease in humans 8,29 , do not play a pathogenic role. In a previous study immunization against aldehyde-modified laminin, another extracellular matrix protein present in basement proteins, resulted in increased atherosclerosis in apoE −/− mice 2 .…”

Section: Discussionmentioning

confidence: 97%

“…Collagen type IV is one of the major components of basement membranes underlying endothelial cells and surrounding smooth muscle cells 28 . Observational studies have identified associations between autoantibodies against collagen type IV and risk for development of cardiovascular disease 8,29 . In the present paper we investigated the effect on an immune response against the basement membrane collagen type IV on atherosclerotic disease.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study we found that MDA-collagen type IV was increased in carotid plaques from patients with cerebrovascular symptoms 7 . Furthermore, antibodies against MDA-collagen type IV were associated with increased risk for myocardial infarction 8 , indicating that immune responses against the basement membrane could be of importance for cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

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Activation of immune responses against the basement membrane component collagen type IV does not affect the development of atherosclerosis in ApoE-deficient mice

Vallejo

Dunér

et al. 2019

Sci Rep

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Oxidation of low-density lipoprotein (LDL) in the arterial extracellular matrix results in malondialdehyde (MDA)-modifications of surrounding matrix proteins. We have recently demonstrated an association between high levels of autoantibodies against MDA-modified collagen type IV and risk for development of myocardial infarction. Collagen type IV is an important component of the endothelial basement membrane and influences smooth muscle cell function. We hypothesized that immune responses against collagen type IV could contribute to vascular injury affecting the development of atherosclerosis. To investigate this possibility, we induced an antibody-response against collagen type IV in apolipoprotein E (Apo E)-deficient mice. Female ApoE −/− mice on C57BL/6 background were immunized with α1α2 type IV collagen chain peptides linked to the immune-enhancer PADRE, PADRE alone or PBS at 12 weeks of age with three subsequent booster injections before the mice were killed at 23 weeks of age. Immunization of PADRE alone induced autoantibodies against PADRE, increased IL-4 secretion from splenocytes and reduced SMC content in the subvalvular plaques. Immunization with peptides of α1α2 type IV collagen chains induced a strong IgG1antibody response against collagen type IV peptides without affecting the distribution of T cell populations, plasma cytokine or lipid levels. There were no differences in atherosclerotic plaque development between collagen α1α2(IV)-PADRE immunized mice and control mice. Our findings demonstrate that the presence of antibodies against the basement membrane component collagen type IV does not affect atherosclerosis development in ApoE −/− mice. This suggests that the association between autoantibodies against collagen type IV and risk for myocardial infarction found in humans does not reflect a pathogenic role of these autoantibodies.

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