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      Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft

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      Author(s)
      Cayci, C.
      Wahlquist, T. C.
      Seckin, S. I.
      Ozcan, V.
      Tekinay, A. B.
      Martens, T. P.
      Oz, M. C.
      Ascherman, J. A.
      Date
      2010
      Source Title
      Annals of Plastic Surgery
      Print ISSN
      0148-7043
      Publisher
      Lippincott Williams & Wilkins
      Volume
      64
      Issue
      1
      Pages
      105 - 113
      Language
      English
      Type
      Article
      Item Usage Stats
      210
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      259
      downloads
      Abstract
      Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFα, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 ± 2.3 vs. 35.6 ± 2.6 μm in control group; P < 0.001). The levels of PDGF-BB, and TNFα were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% ± 0.03% versus 0.39% ± 0.05% in control group, P < 0.001), TNFα (21.2% ± 0.8% vs. 36.1% ± 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% ± 0.03% vs. 0.57% ± 0.09% in control group, P < 0.001], TNFα [25.5% ± 1.8% vs. 45.0% ± 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% ± 2.8% vs. 18.7% ± 3.7% in control group, P < 0.05), and at 4 weeks (17.5% ± 2.6% vs. 31.1% ± 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFα levels and the resulting down-regulation of smooth muscle cells' migration and proliferation.
      Keywords
      Animals
      Antioxidants/pharmacology
      Antioxidants/therapeutic use
      Drug Administration Schedule
      Femoral Artery/surgery
      Flavanones/pharmacology
      Flavanones/therapeutic use
      Hyperplasia/drug therapy
      Hyperplasia/pathology
      Immunohistochemistry
      Postoperative care
      Rats
      Rats, Sprague-Dawley
      Reconstructive Surgical Procedures/methods
      Transplantation, Autologous
      Tunica Intima/drug effects
      Tunica Intima/pathology
      Veins/transplantation
      Permalink
      http://hdl.handle.net/11693/22486
      Published Version (Please cite this version)
      http://dx.doi.org/10.1097/SAP.0b013e31819b03cd
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      • Institute of Materials Science and Nanotechnology (UNAM) 2098
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