OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Pharmacologic inhibition of PARP with INO-1001 may be a new concept to prevent neointimal hyperplasia after endarterectomy.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Pharmacologic inhibition of PARP with INO-1001 may be a new concept to prevent neointimal hyperplasia after endarterectomy.
Authors: Perenlei Enkhbaatar; Jianpu Wang; Fiona Saunders; Matthias Lange; Atsumori Hamahata; Sebastian Rehberg; John F Parkinson; Lillian D Traber; David N Herndon; Daniel L Traber Journal: Burns Date: 2011-02-18 Impact factor: 2.744
Authors: Fiona D Saunders; Martin Westphal; Perenlei Enkhbaatar; Jianpu Wang; Konrad Pazdrak; Yoshimitsu Nakano; Atsumori Hamahata; Collette C Jonkam; Matthias Lange; Rhykka L Connelly; Gabriela A Kulp; Robert A Cox; Hal K Hawkins; Frank C Schmalstieg; Eszter Horvath; Csaba Szabo; Lillian D Traber; Elbert Whorton; David N Herndon; Daniel L Traber Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-12-04 Impact factor: 5.464
Authors: Perenlei Enkhbaatar; Rhykka Connelly; Jianpu Wang; Yoshimitsu Nakano; Matthias Lange; Atsumori Hamahata; Eszter Horvath; Csaba Szabo; Stefan Jaroch; Peter Hölscher; Margrit Hillmann; Lillian D Traber; Frank C Schmalstieg; David N Herndon; Daniel L Traber Journal: Crit Care Med Date: 2009-01 Impact factor: 7.598
Authors: Atsumori Hamahata; Perenlei Enkhbaatar; Edward R Kraft; Matthias Lange; Scott W Leonard; Maret G Traber; Robert A Cox; Frank C Schmalstieg; Hal K Hawkins; Elbert B Whorton; Eszter M Horvath; Csaba Szabo; Lillian D Traber; David N Herndon; Daniel L Traber Journal: Free Radic Biol Med Date: 2008-05-03 Impact factor: 7.376