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Dystrophin deficiency reduces atherosclerotic plaque development in ApoE- mice.

Shami A, Knutsson A, Dunér P, Rauch U, Bengtsson E, Tengryd C, Murugesan V, Durbeej M, Gonçalves I, Nilsson J, Hultgårdh-Nilsson A - Sci Rep (2015)

Bottom Line: Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy.ApoE- 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.

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)- 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- mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE- 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.

No MeSH data available.


Related in: MedlinePlus

Decreased immunoreactivity for laminin in low shear stress plaques in ApoE/mdx compared to ApoE mice.Representative images showing laminin immunoreactivity in low shear stress plaques are found in (a,b), and oscillatory shear stress plaques in (c,d). Plaques from ApoE mice are found in (a,c), and plaques from ApoE/mdx mice in (b,d). Quantification are found in e. Nuclei are stained blue with DAPI and autofluorescence is shown in green. Scale bars represent 100 μm and Mann-Whitney U test was used.
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f3: Decreased immunoreactivity for laminin in low shear stress plaques in ApoE/mdx compared to ApoE mice.Representative images showing laminin immunoreactivity in low shear stress plaques are found in (a,b), and oscillatory shear stress plaques in (c,d). Plaques from ApoE mice are found in (a,c), and plaques from ApoE/mdx mice in (b,d). Quantification are found in e. Nuclei are stained blue with DAPI and autofluorescence is shown in green. Scale bars represent 100 μm and Mann-Whitney U test was used.

Mentions: In the smaller low shear stress plaques of ApoE/mdx mice we also found the laminin expression to be altered. Utilizing an antibody against laminin chains α1, β1 and γ1, thereby detecting the vast majority of the laminin isoforms, we found that low, but not oscillatory, shear stress carotid plaques from ApoE/mdx mice contained less laminin compared to plaques from ApoE mice (p = 0.0004, Fig. 3). Laminin-positive immunoreactivity was typically found in the media and in the plaque region facing the vessel lumen.


Dystrophin deficiency reduces atherosclerotic plaque development in ApoE- mice.

Shami A, Knutsson A, Dunér P, Rauch U, Bengtsson E, Tengryd C, Murugesan V, Durbeej M, Gonçalves I, Nilsson J, Hultgårdh-Nilsson A - Sci Rep (2015)

Decreased immunoreactivity for laminin in low shear stress plaques in ApoE/mdx compared to ApoE mice.Representative images showing laminin immunoreactivity in low shear stress plaques are found in (a,b), and oscillatory shear stress plaques in (c,d). Plaques from ApoE mice are found in (a,c), and plaques from ApoE/mdx mice in (b,d). Quantification are found in e. Nuclei are stained blue with DAPI and autofluorescence is shown in green. Scale bars represent 100 μm and Mann-Whitney U test was used.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4561962&req=5

f3: Decreased immunoreactivity for laminin in low shear stress plaques in ApoE/mdx compared to ApoE mice.Representative images showing laminin immunoreactivity in low shear stress plaques are found in (a,b), and oscillatory shear stress plaques in (c,d). Plaques from ApoE mice are found in (a,c), and plaques from ApoE/mdx mice in (b,d). Quantification are found in e. Nuclei are stained blue with DAPI and autofluorescence is shown in green. Scale bars represent 100 μm and Mann-Whitney U test was used.
Mentions: In the smaller low shear stress plaques of ApoE/mdx mice we also found the laminin expression to be altered. Utilizing an antibody against laminin chains α1, β1 and γ1, thereby detecting the vast majority of the laminin isoforms, we found that low, but not oscillatory, shear stress carotid plaques from ApoE/mdx mice contained less laminin compared to plaques from ApoE mice (p = 0.0004, Fig. 3). Laminin-positive immunoreactivity was typically found in the media and in the plaque region facing the vessel lumen.

Bottom Line: Dystrophin of the dystrophin-glycoprotein complex connects the actin cytoskeleton to basement membranes and loss of dystrophin results in Duchenne muscular dystrophy.ApoE- 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden.

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)- 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- mdx mice demonstrated reduced infiltration of CD3(+) T cells, less laminin and a higher SMC content. ApoE- 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.

No MeSH data available.


Related in: MedlinePlus