Opposite effects of vascular irradiation on inflammatory response and apoptosis induction in the vessel wall layers via the peroxynitrite-poly(ADP- ribose) polymerase pathway

Carsten J. Beller, Eszter Horvath, Jens Kosse, Alexander Becker, Tamás Radovits, Robert Krempien, Irina Berger, Siegfried Hagl, Csaba Szabó, Gábor Szabó

    Research output: Contribution to journalArticle

    2 Scopus citations

    Abstract

    Purpose: We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite - poly(ADPribose) polymerase (PARP) pathway in inflammatory response and apoptosis induction after vascular gamma irradiation. Methods: Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or 20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10). Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n = 10) to distinguish between primary effects of vascular injury and secondary effects due to irradiation. Results: After 21 days, neointima formation was significantly suppressed after irradiation (control: 0.07 mm2 ± 0.04 mm2, 15 Gy: 0.003 mm 2 ± 0.004 mm2, 20 Gy: 0.001 mm2 ± 0.0006 mm2, P< 0.0001). However, a significant inflammation of the vessel wall with focal wall necrosis was detected (control: 0.2 ± 0.15, 15 Gy: 0.82 ± 1.2, 20 Gy: 1.25 ± 0.86, P= 0.003). Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups. Conclusion: Activation of the peroxynitrite-PARP pathway was demonstrated during neointima proliferation in a rat model of surgical vascular injury. Vascular irradiation suppressed neointima formation, but induced significant activation of the peroxynitrite - PARP pathway in the outer vessel wall layers concomitant to inflammation and focal wall necrosis. This may contribute to adverse effects of vascular irradiation such as fibrosis and constrictive remodeling.

    Original languageEnglish (US)
    Pages (from-to)8-16
    Number of pages9
    JournalClinical Research in Cardiology
    Volume96
    Issue number1
    DOIs
    StatePublished - Jan 1 2007

    Keywords

    • Apoptosis
    • Inflammation
    • Irradiation
    • Peroxynitrite-PARP pathway
    • Restenosis

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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