title: Regulation of vascular smooth muscle cell proliferation by nuclear orphan receptor Nur77.
abstract: It has been reported that Nur77 over-expresses in arteriosclerotic lesions and has both pro- and anti-proliferative effects on vascular smooth muscle cells (VSMCs). We investigated the physiological function of Nur77 on proliferation in VSMCs and the effects of atorvastatin on the expression of Nur77. Platelet-derived growth factor (PDGF), a key growth factor mediating VSMC proliferation in atherogenesis and post-angioplasty restenosis, was employed to induce the transcriptional regulation of Nur77 expression in VSMCs and rat carotid artery post-angioplasty restenosis models were used to investigate the effect of atorvastatin on the expression of Nur77 by immunohistochemistry, RT-PCR, and western blot methods. In cell models, we found that PDGF-B induced Nur77 mRNA expression and protein expression through ERK-MAPK-dependent signaling pathways, and atorvastatin attenuated the expression of Nur77 induced by PDGF-B. In the rat model, our data showed Nur77 was up-regulated in neointima, but down-regulated by atorvastatin. Our results indicate that Nur77 promotes VSMC proliferation, and down-regulation of Nur77 by atorvastatin suggests a novel therapy strategy for atherogenesis based on suppression of VSMC proliferation.
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No 1277 Jiefang Avenue, Wuhan, 430020 Hubei, China.
authors.forename: Liyue
authors.initials: L
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Gong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
chemical_list: D006538:Heptanoic Acids; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin
references.citation: Circ Res. 1995 Sep;77(3):445-65
references.pmid: 7641318
references.citation: Circ Res. 2005 Feb 4;96(2):172-9
references.pmid: 15625285
references.citation: Curr Med Chem Cardiovasc Hematol Agents. 2005 Jul;3(3):195-201
references.pmid: 15974884
references.citation: J Am Soc Nephrol. 1999 Sep;10(9):1880-90
references.pmid: 10477139
references.citation: Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):2002-7
references.pmid: 14525795
references.citation: Circulation. 2000 Mar 21;101(11):1311-8
references.pmid: 10725292
references.citation: Cell. 2004 Feb 20;116(4):527-40
references.pmid: 14980220
references.citation: Circulation. 2002 Sep 17;106(12):1530-5
references.pmid: 12234960
references.citation: J Biol Chem. 1999 Jul 30;274(31):21926-31
references.pmid: 10419514
references.citation: Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1769-76
references.pmid: 12426203
references.citation: J Cardiovasc Pharmacol. 2005 May;45(5):468-75
references.pmid: 15821443
references.citation: J Biol Chem. 2005 Aug 12;280(32):29256-62
references.pmid: 15964844
references.citation: Cell. 1995 May 19;81(4):541-50
references.pmid: 7758108
references.citation: Circ Res. 2003 Jan 10;92(1):96-103
references.pmid: 12522126
references.citation: Circ Res. 2005 Apr 15;96(7):e59-67
references.pmid: 15790955
references.citation: J Biol Chem. 2001 Nov 16;276(46):43277-84
references.pmid: 11553630
references.citation: FASEB J. 2001 Sep;15(11):1989-95
references.pmid: 11532979
references.citation: Ann N Y Acad Sci. 1995 Sep 7;766:416-30
references.pmid: 7486687
references.citation: Circ Res. 2004 Dec 10;95(12):e110-23
references.pmid: 15539633
references.citation: J Clin Invest. 1996 Oct 15;98(8):1897-905
references.pmid: 8878442
references.citation: Science. 2001 Nov 30;294(5548):1866-70
references.pmid: 11729302
references.citation: Exp Cell Res. 2003 Oct 15;290(1):28-37
references.pmid: 14516785
references.citation: Circulation. 2005 May 3;111(17):2257-73
references.pmid: 15867193
references.citation: Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1712-9
references.pmid: 11701455
references.citation: J Am Coll Cardiol. 2000 Nov 1;36(5):1691-7
references.pmid: 11079678
references.citation: Nucleic Acids Res. 2004 Oct 05;32(17):5280-90
references.pmid: 15466594
references.citation: Cell Death Differ. 2006 Feb;13(2):293-300
references.pmid: 16082387
references.citation: Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2288-94
references.pmid: 16873729
references.citation: Nat Med. 2002 Nov;8(11):1257-62
references.pmid: 12411953
references.citation: Circulation. 1998 Jul 7;98(1):82-9
references.pmid: 9665064
references.citation: Nat Med. 2002 Nov;8(11):1249-56
references.pmid: 12411952
references.citation: Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1535-40
references.pmid: 12842839
references.citation: J Am Coll Cardiol. 2000 Jan;35(1):214-21
references.pmid: 10636283
references.citation: EMBO J. 2003 Dec 15;22(24):6526-36
references.pmid: 14657025