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 Szabo, Gábor Szabó

Research output: Contribution to journalArticle

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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 2007
Externally publishedYes

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Administrative data processing
Neointima
Peroxynitrous Acid
Poly(ADP-ribose) Polymerases
Cell death
Blood Vessels
Vascular System Injuries
Irradiation
Rats
Necrosis
Apoptosis Inducing Factor
Staining and Labeling
Poly Adenosine Diphosphate Ribose
Inflammation
Anatomic Models
Adventitia
Chemical activation
Carotid Endarterectomy
Intraoperative Complications
Sprague Dawley Rats

Keywords

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

ASJC Scopus subject areas

  • Mechanics of Materials
  • Computational Mechanics

Cite this

Opposite effects of vascular irradiation on inflammatory response and apoptosis induction in the vessel wall layers via the peroxynitrite-poly(ADP- ribose) polymerase pathway. / Beller, Carsten J.; Horvath, Eszter; Kosse, Jens; Becker, Alexander; Radovits, Tamás; Krempien, Robert; Berger, Irina; Hagl, Siegfried; Szabo, Csaba; Szabó, Gábor.

In: Clinical Research in Cardiology, Vol. 96, No. 1, 01.2007, p. 8-16.

Research output: Contribution to journalArticle

Beller, Carsten J. ; Horvath, Eszter ; Kosse, Jens ; Becker, Alexander ; Radovits, Tamás ; Krempien, Robert ; Berger, Irina ; Hagl, Siegfried ; Szabo, Csaba ; Szabó, Gábor. / Opposite effects of vascular irradiation on inflammatory response and apoptosis induction in the vessel wall layers via the peroxynitrite-poly(ADP- ribose) polymerase pathway. In: Clinical Research in Cardiology. 2007 ; Vol. 96, No. 1. pp. 8-16.
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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.",
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AU - Horvath, Eszter

AU - Kosse, Jens

AU - Becker, Alexander

AU - Radovits, Tamás

AU - Krempien, Robert

AU - Berger, Irina

AU - Hagl, Siegfried

AU - Szabo, Csaba

AU - Szabó, Gábor

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N2 - 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.

AB - 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.

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