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

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 mm(2) +/- 0.04 mm(2), 15 Gy: 0.003 mm(2) +/- 0.004 mm(2), 20 Gy: 0.001 mm(2) +/- 0.0006 mm(2), 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.

• Authors: Carsten J Beller, Eszter Horvath, Jens Kosse, Alexander Becker, Tamás Radovits, Robert Krempien, Irina Berger, Siegfried Hagl, Csaba Szabó, Gábor Szabó
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 96 Issue 1 Pg. 8-16 (Jan 2007) ISSN: 1861-0684 [Print] Germany
• PMID: 17021679 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peroxynitrous Acid
• Poly(ADP-ribose) Polymerases

Topics

• Animals
• Apoptosis (radiation effects)
• Blood Vessels (injuries, pathology, radiation effects)
• Disease Models, Animal
• Endarterectomy, Carotid (adverse effects)
• Gamma Rays (adverse effects)
• Immunohistochemistry
• Male
• Peroxynitrous Acid (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Radiation Injuries, Experimental
• Rats
• Rats, Sprague-Dawley
• Tunica Intima (injuries, pathology, radiation effects)
• Vascular Diseases (etiology)