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

Vallejo, J.; Dunér, P.; To, F.; Engelbertsen, D.; Gonçalves, I.; Nilsson, J.; Bengtsson, E.

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

Mark

Vallejo, J. ^LU ; Dunér, P. ^LU ; To, F. ^LU ; Engelbertsen, D. ^LU ; Gonçalves, I. ^LU

; Nilsson, J. ^LU and Bengtsson, E. ^LU

(2019) In Scientific Reports 9(1).

Abstract: 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... (More); 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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Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/598f5daf-7e20-4e10-b60d-c1c177db127e

author

Vallejo, J. ^LU ; Dunér, P. ^LU ; To, F. ^LU ; Engelbertsen, D. ^LU ; Gonçalves, I. ^LU

; Nilsson, J. ^LU and Bengtsson, E. ^LU

organization

publishing date

2019-04-12

type

Contribution to journal

publication status

published

subject

Rheumatology and Autoimmunity

in

Scientific Reports

volume

9

issue

1

article number

5964

publisher

Nature Publishing Group

external identifiers

pmid:30979943
scopus:85064349989

ISSN

2045-2322

DOI

10.1038/s41598-019-42375-8

language

English

LU publication?

yes

id

598f5daf-7e20-4e10-b60d-c1c177db127e

date added to LUP

2019-05-02 13:08:32

date last changed

2024-02-14 22:50:49

@article{598f5daf-7e20-4e10-b60d-c1c177db127e,
  abstract     = {{<p><br>
                                                         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                             <br>
                            <sup>−/−</sup><br>
                                                          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                             <br>
                            <sup>−/−</sup><br>
                                                          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.                         <br>
                        </p>}},
  author       = {{Vallejo, J. and Dunér, P. and To, F. and Engelbertsen, D. and Gonçalves, I. and Nilsson, J. and Bengtsson, E.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Activation of immune responses against the basement membrane component collagen type IV does not affect the development of atherosclerosis in ApoE-deficient mice}},
  url          = {{http://dx.doi.org/10.1038/s41598-019-42375-8}},
  doi          = {{10.1038/s41598-019-42375-8}},
  volume       = {{9}},
  year         = {{2019}},
}

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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