Activation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase pathway during neointima proliferation: a new target to prevent restenosis after endarterectomy

Journal of Vascular Surgery
Carsten J BellerG Szabó

Abstract

In a rat model of endarterectomy, we investigated the potential role of the peroxynitrite-poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) pathway in neointima formation and the effect of pharmacologic inhibition of PARP on vascular remodeling. Carotid endarterectomy was performed in male Sprague-Dawley rats by incision of the left carotid artery with removal of intima. Three groups were studied: sham-operated rats (n = 10), control rats with endarterectomy (n = 10) or rats with endarterectomy treated with the PARP inhibitor, INO-1001 (5 mg/kg daily) postoperatively (n =10). After 21 days, neointima formation and vascular remodeling were assessed. Immunohistochemistry analysis demonstrated activation of the peroxynitrite-PARP pathway with significant staining for nitrotyrosine, poly(ADP-ribose), and nuclear translocation of apoptosis-inducing factor (AIF) in the neointima of the control group. Treatment with INO-1001 significantly reduced the neointima area (0.024 mm2 +/- 0.019 mm2 vs 0.089 mm2 +/- 0.033 mm2 in the control group), the neointima/media thickness ratio (0.81 +/- 0.05 vs 2.76 +/- 1.57 in the control group), and the inflammation score (0.1 +/- 0.07 vs 0.3 +/- 0.12 in the control group) after endarterectomy....Continue Reading

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Citations

Dec 4, 2008·Critical Care Medicine·Perenlei EnkhbaatarDaniel L Traber
Nov 2, 2007·Clinical and Experimental Pharmacology & Physiology·Song-Jie LiaoAlex F Chen
Dec 8, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fiona D SaundersDaniel L Traber
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
May 26, 2009·The Journal of Thoracic and Cardiovascular Surgery·Kristóf HirschbergGábor Szabó
Feb 22, 2011·Burns : Journal of the International Society for Burn Injuries·Perenlei EnkhbaatarDaniel L Traber
May 4, 2010·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·K HirschbergG Szabó
Feb 24, 2015·The International Journal of Cardiovascular Imaging·Pierleone LucatelliLuca Saba
Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Jun 5, 2008·The Journal of Pharmacology and Experimental Therapeutics·Lorraine YauPeter Zahradka
Feb 17, 2017·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Sevil Korkmaz-IcözGábor Szabó
Aug 28, 2021·Progress in Lipid Research·Magdolna SzántóPeter Bai

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