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PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels

OBJECTIVE: Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood. METHODS...

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Autores principales: Erbel, C, Achenbach, J, Akhavanpoor, M, Dengler, TJ, Lasitschka, F, Gleissner, CA, Bea, F, Katus, HA, Szabo, G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351988/
https://www.ncbi.nlm.nih.gov/pubmed/21813379
http://dx.doi.org/10.1186/2047-783X-16-8-367
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author Erbel, C
Achenbach, J
Akhavanpoor, M
Dengler, TJ
Lasitschka, F
Gleissner, CA
Bea, F
Katus, HA
Szabo, G
author_facet Erbel, C
Achenbach, J
Akhavanpoor, M
Dengler, TJ
Lasitschka, F
Gleissner, CA
Bea, F
Katus, HA
Szabo, G
author_sort Erbel, C
collection PubMed
description OBJECTIVE: Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood. METHODS: Male Apoe(-/- )mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks. RESULTS: Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03). CONCLUSIONS: Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL.
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spelling pubmed-33519882012-05-16 PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels Erbel, C Achenbach, J Akhavanpoor, M Dengler, TJ Lasitschka, F Gleissner, CA Bea, F Katus, HA Szabo, G Eur J Med Res Research OBJECTIVE: Atherosclerosis is a chronic inflammatory process. Poly(ADP-ribose) polymerase-1 (PARP), a nuclear enzyme linked to DNA repair, has been shown to be involved in atherogenesis; however, the effects on dendritic cells, T cells and serum auto-antibody levels are not fully understood. METHODS: Male Apoe(-/- )mice on a western diet were treated with the PARP inhibitor 1NO-1001 (n = 15), while the control group (n = 15) received 5% glucose solution for 10 weeks. RESULTS: Inhibition of PARP markedly reduced atherosclerotic lesion development (p = 0.001). Immunohistochemistry and mRNA analysis revealed a reduced inflammatory compound inside the lesion. Focusing on dendritic cells, INO-1001 reduced number of cells (p = 0.04), grade of activation, represented by I/12 (p = 0.04) and Cd83 (p = 0.03), and grade of attraction, represented by Mip3α (p = 0.02) in the plaque. Furthermore, INO-1001 decreased number of T lymphocyte (p = 0.003) in the lesion and grade of activation after stimulation with oxLDL in vitro. Moreover, serum IgM antibody levels to oxLDL were significantly lower in INO-1001 treated mice (p = 0.03). CONCLUSIONS: Functional blockade of PARP by INO-1001 reduces atherosclerotic lesion development. The anti-atherogenic effect is beside already known mechanisms also moderated due to modulation of DC and T cell invasion and activation, DC attraction as well as IgM antibody levels to oxLDL. BioMed Central 2011-08-08 /pmc/articles/PMC3351988/ /pubmed/21813379 http://dx.doi.org/10.1186/2047-783X-16-8-367 Text en Copyright ©2011 I Holzapfel Publishers
spellingShingle Research
Erbel, C
Achenbach, J
Akhavanpoor, M
Dengler, TJ
Lasitschka, F
Gleissner, CA
Bea, F
Katus, HA
Szabo, G
PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title_full PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title_fullStr PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title_full_unstemmed PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title_short PARP inhibition in atherosclerosis and its effects on dendritic cells, T cells and auto-antibody levels
title_sort parp inhibition in atherosclerosis and its effects on dendritic cells, t cells and auto-antibody levels
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351988/
https://www.ncbi.nlm.nih.gov/pubmed/21813379
http://dx.doi.org/10.1186/2047-783X-16-8-367
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