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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

Decrease in T cell plaque content.The number of T cells relative to plaque size was decreased in low shear stress plaque from ApoE/mdx compared to ApoE mice (as determined through Mann-Whitney U test).
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f4: Decrease in T cell plaque content.The number of T cells relative to plaque size was decreased in low shear stress plaque from ApoE/mdx compared to ApoE mice (as determined through Mann-Whitney U test).

Mentions: To determine if the reduced development of atherosclerosis in ApoE/mdx mice involved changes in vascular inflammation we analysed the macrophage and T cell accumulation in plaques from the low and oscillatory shear stress region of the carotid artery. Plaques from ApoE/mdx demonstrated a marked reduction in CD3+ T cell numbers in both low shear stress (0 (0–3.8) versus 5.0 (1.0–12.7) cells/0.1 mm2, p = 0.02 and oscillatory shear stress lesions (1.9 (1.0–4.2) versus 3.8 (2.2–8.1) cells/0.1 mm2, p = 0.04) (Fig. 4 and Supplementary Fig. S7), while there was no difference in macrophage immunoreactivity (Supplementary Fig. S6).


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)

Decrease in T cell plaque content.The number of T cells relative to plaque size was decreased in low shear stress plaque from ApoE/mdx compared to ApoE mice (as determined through Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Decrease in T cell plaque content.The number of T cells relative to plaque size was decreased in low shear stress plaque from ApoE/mdx compared to ApoE mice (as determined through Mann-Whitney U test).
Mentions: To determine if the reduced development of atherosclerosis in ApoE/mdx mice involved changes in vascular inflammation we analysed the macrophage and T cell accumulation in plaques from the low and oscillatory shear stress region of the carotid artery. Plaques from ApoE/mdx demonstrated a marked reduction in CD3+ T cell numbers in both low shear stress (0 (0–3.8) versus 5.0 (1.0–12.7) cells/0.1 mm2, p = 0.02 and oscillatory shear stress lesions (1.9 (1.0–4.2) versus 3.8 (2.2–8.1) cells/0.1 mm2, p = 0.04) (Fig. 4 and Supplementary Fig. S7), while there was no difference in macrophage immunoreactivity (Supplementary Fig. S6).

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