title: Role of complement 3a in the synthetic phenotype and angiotensin II-production in vascular smooth muscle cells from spontaneously hypertensive rats.
abstract: BACKGROUND
  Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMCs) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II)-production. To evaluate the contribution of complement 3 (C3) or C3a toward these abnormalities in SHR, we examined effects of a C3a receptor inhibitor on proliferation, phenotype, and Ang II-production in VSMCs from SHR and Wistar-Kyoto (WKY) rats.
  
  
  METHODS
  Expression of pre-pro-C3 messenger RNA (mRNA) and C3 protein was evaluated by reverse transcription-PCR and western blot analyses, and C3a receptor mRNA was evaluated by reverse transcription-PCR analysis in quiescent VSMCs from SHR and WKY rats. We examined the effects of the C3a inhibitor, SB290157, on proliferation and the expression of phenotype-marker and Krueppel-like factor 5 (KLF-5) mRNAs in VSMCs from SHR and WKY rats. We examined effects of C3a receptor inhibitor, SB290157, on Ang II-production in conditioned medium of VSMCs from SHR and WKY rats by a radioimmunoassay.
  
  
  RESULTS
  Expression of pre-pro-C3 mRNA and C3 protein was significantly higher in SHR VSMCs than WKY VSMCs. SB290157 significantly inhibited proliferation of VSMCs from SHR, but not in cells from WKY rats. Relative to WKY VSMCs, SB290157 significantly increased the low expression of SM22α mRNA and decreased the high expression of osteopontin mRNA in SHR VSMCs. SB290157 significantly decreased the high expression of KLF-5 and Ang II-production in VSMCs from SHR, but not in cells from WKY rats.
  
  
  CONCLUSIONS
  C3a induces exaggerated growth, a synthetic phenotype and Ang II-production in SHR-derived VSMCs. C3a may be primarily involved in cardiovascular remodeling in hypertension.
authors.affiliation: Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Morito
authors.initials: M
authors.lastname: Endo
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ikeda
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xueli
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis* / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D015926:Complement C3a / Q000502:physiology*; D006973:Hypertension / Q000276:immunology* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011951:Receptors, Complement / Q000037:antagonists & inhibitors* / Q000187:drug effects
chemical_list: D001559:Benzhydryl Compounds; C492215:Klf5 protein, rat; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D011951:Receptors, Complement; C431907:SB 290157; C085567:complement C3a receptor; D000804:Angiotensin II; D015926:Complement C3a; D001120:Arginine
references.citation: J Biol Chem. 1990 Aug 5;265(22):13042-6
references.pmid: 2376586
references.citation: Immunol Rev. 2001 Apr;180:35-48
references.pmid: 11414361
references.citation: J Hypertens. 1999 Aug;17(8):1099-107
references.pmid: 10466465
references.citation: Jpn Heart J. 1999 Nov;40(6):803-18
references.pmid: 10737564
references.citation: Endocrinology. 1991 Nov;129(5):2774-9
references.pmid: 1935807
references.citation: J Cell Physiol. 2003 Aug;196(2):284-92
references.pmid: 12811821
references.citation: Immunobiology. 1999 Feb;200(1):92-105
references.pmid: 10084698
references.citation: J Hypertens. 2002 Jul;20(7):1323-33
references.pmid: 12131529
references.citation: Gene. 1990 Sep 14;93(2):271-5
references.pmid: 1699848
references.citation: Circulation. 2002 Jun 25;105(25):3025-31
references.pmid: 12081998
references.citation: Arterioscler Thromb Vasc Biol. 1999 May;19(5):1210-7
references.pmid: 10323771
references.citation: Clin Exp Hypertens A. 1984;6(4):755-81
references.pmid: 6233050
references.citation: Immunology. 1996 Oct;89(2):183-8
references.pmid: 8943712
references.citation: Circ Res. 1974 Nov;35(5):775-81
references.pmid: 4371062
references.citation: Hypertension. 1986 Jun;8(6):520-5
references.pmid: 3710557
references.citation: Hypertension. 2004 Jul;44(1):42-7
references.pmid: 15136559
references.citation: Am Heart J. 1987 Oct;114(4 Pt 2):938-48
references.pmid: 3661386
references.citation: J Cell Physiol. 2007 Nov;213(2):495-501
references.pmid: 17520688
references.citation: Arterioscler Thromb Vasc Biol. 2000 Jun;20(6):1500-5
references.pmid: 10845864
references.citation: Biochem Biophys Res Commun. 2008 Mar 7;367(2):468-73
references.pmid: 18178156
references.citation: Circ Res. 1999 Jul 23;85(2):182-91
references.pmid: 10417400
references.citation: J Thromb Haemost. 2005 Aug;3(8):1569-76
references.pmid: 16102021
references.citation: Hypertension. 1989 Jun;13(6 Pt 1):589-97
references.pmid: 2786847
references.citation: Lab Invest. 1985 Nov;53(5):556-62
references.pmid: 4057952
references.citation: Adv Immunol. 1978;26:1-53
references.pmid: 358800
references.citation: FASEB J. 2003 Jun;17(9):1003-14
references.pmid: 12773483
references.citation: Proc Natl Acad Sci U S A. 1985 Feb;82(3):708-12
references.pmid: 2579379
references.citation: J Immunol. 2009 Mar 15;182(6):3827-36
references.pmid: 19265162
references.citation: Clin Sci Mol Med Suppl. 1978 Dec;4:3s-22s
references.pmid: 153216