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

Author:
  • Annelie Shami
  • Anki Knutsson
  • Pontus Dunér
  • Uwe Rauch
  • Eva Bengtsson
  • Christoffer Tengryd
  • Vignesh Murugesan
  • Madeleine Durbeej-Hjalt
  • Isabel Goncalves
  • Jan Nilsson
  • Anna Hultgårdh
Publishing year: 2015
Language: English
Publication/Series: Scientific Reports
Volume: 5
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • Vessel Wall Biology
  • Cardiovascular Research - Immunity and Athersosclerosis
  • Muscle Biology
  • ISSN: 2045-2322

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