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

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Summary

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 mm2 ± 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.

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Authors and Affiliations

  1. Department of Cardiac Surgery, University of Heidelberg, INF 326, 69120, Heidelberg, Germany

    Carsten J. Beller, Jens Kosse, Alexander Becker, Tamás Radovits, Siegfried Hagl & Gábor Szabó

  2. Department of Human Physiology and Clinical Experimental Research, Semmelweis University, Üllőút 78./A, 1082, Budapest, Hungary

    Eszter Horvath & Csaba Szabó

  3. Department of Clinical Radiology, University of Heidelberg, INF 400, 69120, Heidelberg, Germany

    Robert Krempien

  4. Department of Pathology, University of Heidelberg, INF 220, 69120, Heidelberg, Germany

    Irina Berger

Authors
  1. Carsten J. Beller
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  2. Eszter Horvath
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  3. Jens Kosse
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  4. Alexander Becker
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  5. Tamás Radovits
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  7. Irina Berger
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  8. Siegfried Hagl
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  9. Csaba Szabó
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  10. Gábor Szabó
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Corresponding author

Correspondence to Carsten J. Beller.

Additional information

Carsten J. Beller and Eszter Horvath contributed equally to this work.

This work was supported by a Grant from the German Research Foundation (SFB 414) to CJB, RK, SH, GS and a Grant from the Hungarian Research Fund (OTKA M041541) to CS.

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Beller, C.J., Horvath, E., Kosse, J. et al. Opposite effects of vascular irradiation on inflammatory response and apoptosis induction in the vessel wall layers via the peroxynitrite-poly(ADP-ribose) polymerase pathway. Clin Res Cardiol 96, 8–16 (2007). https://doi.org/10.1007/s00392-006-0446-z

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  • DOI: https://doi.org/10.1007/s00392-006-0446-z

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