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Dystrophin deficiency reduces atherosclerotic plaque development in ApoE-null mice.

Shami, Annelie LU ; Knutsson, Anki LU ; Dunér, Pontus LU ; Rauch, Uwe LU ; Bengtsson, Eva LU ; Tengryd, Christoffer LU ; Murugesan, Vignesh LU ; Durbeej-Hjalt, Madeleine LU ; Goncalves, Isabel LU and Nilsson, Jan LU , et al. (2015) In Scientific Reports 5.
Abstract
Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)-null mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory... (More)
Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)-null mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE-null mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE-null mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells. (Less)
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Scientific Reports
volume
5
publisher
Nature Publishing Group
external identifiers
  • pmid:26345322
  • wos:000360800400001
  • scopus:84941055787
ISSN
2045-2322
DOI
10.1038/srep13904
language
English
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yes
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be54acc0-a828-4c8b-a7d7-70c0b8d4d318 (old id 8042951)
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http://www.ncbi.nlm.nih.gov/pubmed/26345322?dopt=Abstract
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2015-10-04 16:48:05
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2017-10-01 04:11:36
@article{be54acc0-a828-4c8b-a7d7-70c0b8d4d318,
  abstract     = {Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy. We have previously shown injury-induced neointima formation of the carotid artery in mice with the mdx mutation (causing dystrophin deficiency) to be increased. To investigate the role of dystrophin in intimal recruitment of smooth muscle cells (SMCs) that maintains plaque stability in atherosclerosis we applied a shear stress-modifying cast around the carotid artery of apolipoprotein E (ApoE)-null mice with and without the mdx mutation. The cast induces formation of atherosclerotic plaques of inflammatory and SMC-rich/fibrous phenotypes in regions of low and oscillatory shear stress, respectively. Unexpectedly, presence of the mdx mutation markedly reduced the development of the inflammatory low shear stress plaques. Further characterization of the low shear stress plaques in ApoE-null mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE-null mdx mice were also found to have a reduced fraction of CD3(+) T cells in the spleen and lower levels of cytokines and monocytes in the circulation. The present study is the first to demonstrate a role for dystrophin in atherosclerosis and unexpectedly shows that this primarily involves immune cells.},
  articleno    = {13904},
  author       = {Shami, Annelie and Knutsson, Anki and Dunér, Pontus and Rauch, Uwe and Bengtsson, Eva and Tengryd, Christoffer and Murugesan, Vignesh and Durbeej-Hjalt, Madeleine and Goncalves, Isabel and Nilsson, Jan and Hultgårdh, Anna},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Dystrophin deficiency reduces atherosclerotic plaque development in ApoE-null mice.},
  url          = {http://dx.doi.org/10.1038/srep13904},
  volume       = {5},
  year         = {2015},
}