Autoantibodies against basement membrane collagen type IV are associated with myocardial infarction

Abstract

BackgroundCollagen type IV is the major constituent of basement membranes underlying endothelial cells and is important for endothelial cell attachment and function. Autoantibodies against native collagen type IV have been found in various autoimmune diseases. Oxidation of LDL in the vascular wall results in the formation of reactive aldehydes, which could modify surrounding matrix proteins. Like oxidized LDL, these modified matrix proteins are likely to induce immune responses. We examined whether autoantibodies against native or aldehyde-modified collagen type IV are associated with myocardial infarction.MethodsIgM and IgG against native and aldehyde-modified collagen type IV were measured by ELISA in serum from 387 survivors of a first myocardial infarction and 387 age- and sex-matched controls.ResultsPost-infarction patients had significantly increased levels of IgM against native collagen type IV, and IgG against native collagen type IV was present at detectable level in 17% of patients as opposed to 7% of controls (p < 0.001). Controlling for major cardiovascular risk factors demonstrated that the presence of IgG against native collagen type IV was associated with myocardial infarction (OR 2.9 (1.6–5.4), p = 0.001). Similarly, subjects in the highest quartile of IgM against native collagen type IV had increased risk of having suffered myocardial infarction (OR 3.11 (1.8–5.4), p < 0.001) after adjusting for cardiovascular risk factors. In contrast, IgG against aldehyde-modified collagen type IV was decreased in myocardial infarction patients, but this association was not independent of established cardiovascular risk factors.ConclusionAutoantibodies against collagen type IV are associated with myocardial infarction independently of traditional cardiovascular risk factors.

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

“…In the present study, the association between high levels of IgG antibodies against MDA-collagen type IV in plasma and increased risk of development of MI was independent of cardiovascular disease risk factors. In a previous study, we showed that IgG antibodies against MDA-collagen type IV was decreased in post-MI patients, although this difference was not independent of traditional risk factors [42]. We cannot exclude the possibility that the increased levels of IgG antibodies against MDAcollagen type IV in patients who later developed MI in the present study might reflect a defence mechanism against atherosclerosis rather than a proatherogenic role of these antibodies.…”

“…In a previous study, we showed that IgG antibodies against MDA-collagen type IV was decreased in post-MI patients, although this difference was not independent of traditional risk factors [42]. In a previous study, we showed that IgG antibodies against MDA-collagen type IV was decreased in post-MI patients, although this difference was not independent of traditional risk factors [42].…”

“…Plates were washed with PBS containing 0.05% Tween 20. Absorbance from wells coated with MDA-collagen type IV was subtracted from absorbance from wells coated with native collagen type IV to exclude antibody binding to native epitopes of MDA-collagen type IV [42]. Absorbance values were normalized relative to a plasma pool present on each plate.…”

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

“…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 .…”

“…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.…”