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


CONCLUSIONS
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.
Beller
Carsten J
CJ
Department of Cardiac Surgery, University of Heidelberg, INF 326, 69120 Heidelberg, Germany. Carsten.Beller@urz.uni-heidelberg.de
Horvath
Eszter
E
Kosse
Jens
J
Becker
Alexander
A
Radovits
Tamás
T
Krempien
Robert
R
Berger
Irina
I
Hagl
Siegfried
S
Szabó
Csaba
C
Szabó
Gábor
G
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001808:Blood Vessels / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*; D004195:Disease Models, Animal; D016894:Endarterectomy, Carotid / Q000009:adverse effects; D005720:Gamma Rays / Q000009:adverse effects*; D007150:Immunohistochemistry; D008297:Male; D030421:Peroxynitrous Acid / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011833:Radiation Injuries, Experimental; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*; D014652:Vascular Diseases / Q000209:etiology
D030421:Peroxynitrous Acid; D011065:Poly(ADP-ribose) Polymerases