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

• Main Authors: Erbel C, Achenbach J, Akhavanpoor M, Dengler TJ, Lasitschka F, Gleissner CA, Bea F, Katus HA, Szabo G
• Format: Article
• Language: English
• Published: BMC 2011-08-01
• Series: European Journal of Medical Research
• Subjects: PARP; atherosclerosis; inflammation; oxLDL; dendritic cells; T cells
• Online Access: http://www.eurjmedres.com/content/16/8/367

<p>Abstract</p> <p>Objective</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 <it>I/12 </it>(p = 0.04) and <it>Cd83 </it>(p = 0.03), and grade of attraction, represented by <it>Mip3α </it>(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).</p> <p>Conclusions</p> <p>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.</p>