title: Salvianolic acid A inhibits angiotensin II-induced proliferation of human umbilical vein endothelial cells by attenuating the production of ROS.
abstract: OBJECTIVE
  To investigate the action of salvianolic acid A (SalA) on angiotensin II (Ang II)-induced proliferation of human umbilical vein endothelial cells (HUVECs) and the possible signaling pathways mediating this action.
  
  
  METHODS
  Cell proliferation was examined with MTT assay. The expression levels of Src phosphorylation (phospho-Src), Akt phosphorylation (phospho-Akt), and NADPH oxidase 4 (Nox4) in HUVECs were determined by Western blot. The production of reactive oxygen species (ROS) was estimated using fluorescence-activated cell sorting (FACS).
  
  
  RESULTS
  SalA (6.25-50 μmol/L) did not affect the viability of HUVECs. Treatment of HUVECs with Ang II (1 μmol/L) markedly increased the cell viability; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) prevented Ang II-induced increase of the cell viability in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) markedly up-regulated the protein expression levels of phospho-Src, phospho-Akt (473) and Nox4; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked all the effects in a concentration-dependent manner. Treatment of HUVECs with Ang II (1 μmol/L) dramatically increased ROS production in HUVECs; pretreatment of HUVECs with SalA (12.5, 25 and 50 μmol/L) blocked the ROS production in a concentration-dependent manner.
  
  
  CONCLUSIONS
  SalA inhibits Ang II-induced proliferation of HUVECs via reducing the expression levels of phospho-Src and phospho-Akt (473), thereby attenuating the production of ROS.
authors.affiliation: Institute of Cardiovascular Disease, Xuzhou Medical College, China.
authors.forename: Luan-luan
authors.initials: LL
authors.lastname: Yang
authors.forename: Dong-ye
authors.initials: DY
authors.lastname: Li
authors.forename: Yan-bin
authors.initials: YB
authors.lastname: Zhang
authors.forename: Man-yi
authors.initials: MY
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Tong-da
authors.initials: TD
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007773:Lactates / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002109:Caffeic Acids; D007773:Lactates; D017382:Reactive Oxygen Species; D000804:Angiotensin II; C066201:salvianolic acid A; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D051057:Proto-Oncogene Proteins c-akt
references.citation: J Asian Nat Prod Res. 2002 Dec;4(4):271-80
references.pmid: 12450255
references.citation: Can J Physiol Pharmacol. 1999 Aug;77(8):606-17
references.pmid: 10543724
references.citation: Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):308-17
references.pmid: 15706079
references.citation: Annu Rev Cell Dev Biol. 1997;13:513-609
references.pmid: 9442882
references.citation: J Cardiovasc Pharmacol. 2010 Feb;55(2):203-12
references.pmid: 20010434
references.citation: Trends Biochem Sci. 2004 May;29(5):233-42
references.pmid: 15130559
references.citation: Eur J Pharmacol. 2009 Aug 1;615(1-3):125-32
references.pmid: 19445921
references.citation: Oncogene. 2002 Nov 7;21(51):7797-807
references.pmid: 12420216
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):981-7
references.pmid: 12663375
references.citation: Free Radic Biol Med. 2003 Jul 15;35(2):117-32
references.pmid: 12853068
references.citation: Circ Res. 2000 Jul 7;87(1):26-32
references.pmid: 10884368
references.citation: Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):745-51
references.pmid: 12006385
references.citation: Phytomedicine. 2002 Jul;9(5):405-9
references.pmid: 12222659
references.citation: World J Gastroenterol. 2000 Jun;6(3):361-364
references.pmid: 11819598
references.citation: Biochem Pharmacol. 1996 May 3;51(9):1237-41
references.pmid: 8645348
references.citation: Free Radic Biol Med. 2003 Nov 1;35(9):1082-100
references.pmid: 14572611
references.citation: Curr Protoc Immunol. 2002 Aug;Chapter 5:Unit 5.4
references.pmid: 18432885
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1014-30
references.pmid: 15475499
references.citation: J Cardiovasc Pharmacol. 2011 Nov;58(5):535-42
references.pmid: 21795988
references.citation: Cell Physiol Biochem. 2001;11(4):173-86
references.pmid: 11509825
references.citation: Biochem Biophys Res Commun. 2008 May 2;369(2):672-8
references.pmid: 18313394
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: Hypertension. 2008 Jul;52(1):143-9
references.pmid: 18474828
references.citation: Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1720-6
references.pmid: 11701456
references.citation: J Pharmacol Exp Ther. 2009 Nov;331(2):404-11
references.pmid: 19692634
references.citation: Circulation. 2004 Jan 20;109(2):227-33
references.pmid: 14718399
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: Physiol Rev. 2007 Jan;87(1):245-313
references.pmid: 17237347
references.citation: Cardiovasc Res. 2006 Jul 15;71(2):226-35
references.pmid: 16781692
references.citation: Lupus. 2000;9(3):189-93
references.pmid: 10805486
references.citation: Am J Physiol. 1999 Feb;276(2):E303-9
references.pmid: 9950790
references.citation: Cell. 2007 Jun 29;129(7):1261-74
references.pmid: 17604717
references.citation: Reproduction. 2008 Jul;136(1):125-30
references.pmid: 18390690
references.citation: FEBS Lett. 2000 Dec 15;486(3):252-6
references.pmid: 11119713
references.citation: J Pharmacol Sci. 2006 Sep;102(1):112-20
references.pmid: 16974068
references.citation: Mol Biol Cell. 2010 Dec;21(23):4287-98
references.pmid: 20943948
references.citation: J Cell Mol Med. 2004 Jan-Mar;8(1):144-52
references.pmid: 15090271
references.citation: Cardiovasc Res. 1999 Oct;44(1):215-22
references.pmid: 10615405
references.citation: J Biol Chem. 2007 Nov 30;282(48):35373-85
references.pmid: 17908694