title: NADPH oxidase p47phox siRNA attenuates adventitial fibroblasts proliferation and migration in apoE(-/-) mouse.
abstract: BACKGROUND
  Reactive oxide species (ROS) derived from NADPH oxidases is involved in atherosclerosis. However, as a key component of NADPH oxidase, how p47phox regulates NADPH oxidases activity, ROS production and adventitial fibroblasts (AFs) function remains unclear.
  
  
  METHODS
  p47phox in aortic arteries of apoE(-/-) mice fed with hyperlipid diet was detected by immunohistochemistry. NADPH oxidase activity, superoxide anion (O2(-)) generation and p47phox expression were analyzed in primary AFs treated by diphenyleneiodonium (DPI). The proliferation and migration of AFs were also analyzed.
  
  
  RESULTS
  p47phox expression was low in the aortic adventitia but high in the site of intimal injury with continuous hyperlipidic diet. Compared to AFs from wild-type mice, AFs derived from apoE(-/-) mice exhibited elevated NADPH oxidase activity, O2(-) production and higher mRNA and protein levels of p47phox, correlated with increased capability of proliferation and migration. DPI inhibited NADPH oxidase activity and AFs proliferation and migration in a dose-dependent manner. In addition, siRNA mediated knockdown of p47phox attenuated the proliferation and migration of AFs derived from apoE(-/-) mice.
  
  
  CONCLUSIONS
  p47phox plays a critical role in the regulation of adventitial fibroblast proliferation and migration and may be a new therapeutic target for neointimal hyperplasia.
authors: Fang
authors: F
authors: Xu
authors: Affiliated Hospital, Binzhou Medical University, 661 Huangheer Road, Binzhou 256603, China. ly_1510@163.com.
authors: Ying
authors: Y
authors: Liu
authors: Lei
authors: L
authors: Shi
authors: Wei
authors: W
authors: Liu
authors: Li
authors: L
authors: Zhang
authors: Hongjing
authors: H
authors: Cai
authors: Jie
authors: J
authors: Qi
authors: Yong
authors: Y
authors: Cui
authors: Weichen
authors: W
authors: Wang
authors: Yejia
authors: Y
authors: Hu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D034741:RNA, Small Interfering; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
references: Antioxid Redox Signal. 2014 Jun 10;20(17):2794-814
references: 24180474
references: Biochem Biophys Res Commun. 2007 Jan 19;352(3):681-8
references: 17141183
references: Hypertension. 2002 Feb;39(2):269-74
references: 11847196
references: Eur J Pharmacol. 2007 Apr 30;561(1-3):121-8
references: 17292348
references: Circulation. 2000 Mar 28;101(12):1362-5
references: 10736277
references: Circ Res. 1998 Apr 20;82(7):810-8
references: 9562441
references: Blood. 1996 Oct 1;88(7):2714-21
references: 8839867
references: Atherosclerosis. 2014 Nov;237(1):208-19
references: 25244505
references: Arterioscler Thromb Vasc Biol. 2001 May;21(5):739-45
references: 11348868
references: Curr Pharm Biotechnol. 2012 Oct;13(13):2435-9
references: 22280417
references: Free Radic Biol Med. 2000 Apr 15;28(8):1232-42
references: 10889453
references: J Clin Invest. 2003 Apr;111(8):1201-9
references: 12697739
references: Arterioscler Thromb Vasc Biol. 1997 Mar;17(3):417-22
references: 9102158
references: J Clin Invest. 2001 Nov;108(10):1513-22
references: 11714743
references: J Leukoc Biol. 1996 Dec;60(6):677-91
references: 8975869
references: Circ Res. 2003 Apr 4;92(6):637-43
references: 12609967
references: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1529-35
references: 10845868
references: Circ Res. 2000 Nov 10;87(10):840-4
references: 11073878
references: Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):21-7
references: 11788456
references: Circulation. 1999 Oct 5;100(14):1494-8
references: 10510050
references: Circulation. 2000 Mar 21;101(11):1234-6
references: 10725280
references: Int J Exp Pathol. 2000 Jun;81(3):173-82
references: 10971738
references: Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):447-53
references: 15591225
references: Am J Physiol Heart Circ Physiol. 2006 May;290(5):H1933-41
references: 16603705
references: Hypertension. 1998 Aug;32(2):331-7
references: 9719063