title: STAT3 and cardiac remodeling.
abstract: Multiple in vitro and in vivo studies showed that the signal transducer and activator of transcription 3 (STAT3) protein is involved in cardiomyocyte protection and hypertrophy and via paracrine pathways impacts on the non-myocyte compartment, i.e., the vasculature and the extracellular matrix. In this regard, STAT3 interacts with a broad range of cellular and molecular mechanisms that direct remodeling processes in cardiac physiology (exercise, pregnancy) and pathophysiology (pressure overload, ischemia/reperfusion, myocardial infarction, and cardiotoxic agents). STAT3 is constitutively activated by a multitude of factors including cytokines, growth factors, neurohormones, mechanical load, and ischemia. It acts as a signaling molecule, a transcription factor and according to latest observations as a mitochondrial protein involved in energy production. In this review, we provide an overview on STAT3 signaling and summarize the current understanding of the role of STAT3 for different aspects of cardiac remodeling obtained from numerous experimental and clinical studies. Finally, we highlight and critically discuss STAT3 signaling as a possible target for future therapeutic approaches in the setting of cardiac remodeling.
authors.affiliation: Department of Cardiology and Angiology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Haghikia
authors.forename: Britta
authors.initials: B
authors.lastname: Stapel
authors.forename: Melanie
authors.initials: M
authors.lastname: Hoch
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
mesh_terms: D000375:Aging; D000804:Angiotensin II; D002311:Cardiomyopathy, Dilated / Q000473:pathology*; D005109:Extracellular Matrix; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D020257:Ventricular Remodeling
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000804:Angiotensin II
references.citation: J Biol Chem. 2008 Feb 15;283(7):3791-8
references.pmid: 18065416
references.citation: Trends Mol Med. 2007 Jan;13(1):4-11
references.pmid: 17118707
references.citation: Circ Res. 2007 Oct 26;101(9):910-8
references.pmid: 17823373
references.citation: Circulation. 1999 Jan 26;99(3):427-33
references.pmid: 9918531
references.citation: Cell Struct Funct. 2006;31(2):53-62
references.pmid: 16988490
references.citation: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1545-56
references.pmid: 19717737
references.citation: Circ Res. 1998 Feb 9;82(2):244-50
references.pmid: 9468195
references.citation: J Biol Chem. 1996 Apr 19;271(16):9535-45
references.pmid: 8621626
references.citation: J Clin Invest. 2002 May;109(9):1143-8
references.pmid: 11994402
references.citation: Circulation. 1976 Jul;54(1):64-70
references.pmid: 1277431
references.citation: Cell. 1999 Apr 16;97(2):189-98
references.pmid: 10219240
references.citation: Biochem Soc Trans. 2006 Dec;34(Pt 6):1028-31
references.pmid: 17073743
references.citation: Circulation. 1986 Nov;74(5):1124-36
references.pmid: 3769170
references.citation: Circulation. 1993 Sep;88(3):1264-72
references.pmid: 8353888
references.citation: Circulation. 1995 Oct 1;92(7):1866-75
references.pmid: 7671371
references.citation: FASEB J. 2006 Oct;20(12):2115-7
references.pmid: 16935931
references.citation: Pharmacol Ther. 2005 Jul;107(1):131-7
references.pmid: 15963355
references.citation: Stem Cells Dev. 2009 Mar;18(2):205-14
references.pmid: 18576943
references.citation: Science. 1994 Apr 1;264(5155):95-8
references.pmid: 8140422
references.citation: Cardiovasc Res. 2005 Oct 1;68(1):109-17
references.pmid: 15978561
references.citation: J Endocrinol. 2002 May;173(2):219-38
references.pmid: 12010630
references.citation: Ann N Y Acad Sci. 2009 Aug;1171:59-76
references.pmid: 19723038
references.citation: Circulation. 2003 Feb 18;107(6):798-802
references.pmid: 12591746
references.citation: Heart Vessels. 2004 Sep;19(5):237-41
references.pmid: 15372299
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9342-7
references.pmid: 12867595
references.citation: Oncogene. 2000 May 15;19(21):2628-37
references.pmid: 10851062
references.citation: J Mol Cell Cardiol. 2002 Nov;34(11):1443-53
references.pmid: 12431443
references.citation: Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1668-73
references.pmid: 12377747
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):315-9
references.pmid: 10618415
references.citation: FASEB J. 2003 Aug;17(11):1562-4
references.pmid: 12824281
references.citation: Cardiovasc Res. 2009 Jul 15;83(2):313-24
references.pmid: 19233863
references.citation: Exp Biol Med (Maywood). 2009 Mar;234(3):246-54
references.pmid: 19144865
references.citation: Circ Res. 2007 Jan 5;100(1):140-6
references.pmid: 17170366
references.citation: J Immunol. 2000 Sep 1;165(5):2798-808
references.pmid: 10946312
references.citation: Circulation. 2002 Sep 17;106(12):1442-6
references.pmid: 12234945
references.citation: J Mol Cell Cardiol. 2004 Mar;36(3):393-404
references.pmid: 15010278
references.citation: Circ Res. 2004 Jul 23;95(2):187-95
references.pmid: 15192020
references.citation: Stem Cells. 2005 Nov-Dec;23(10):1634-42
references.pmid: 16099994
references.citation: Mol Biol Cell. 2008 May;19(5):1893-902
references.pmid: 18287540
references.citation: J Cardiovasc Med (Hagerstown). 2011 Jul;12(7):510-2
references.pmid: 19858731
references.citation: Br J Pharmacol. 2008 Mar;153 Suppl 1:S414-27
references.pmid: 18246092
references.citation: Circ Res. 1999 May 28;84(10):1127-36
references.pmid: 10347087
references.citation: J Cardiovasc Pharmacol. 2007 Aug;50(2):126-41
references.pmid: 17703129
references.citation: Cardiovasc Res. 2004 Oct 1;64(1):61-71
references.pmid: 15364614
references.citation: J Cell Sci. 2005 Oct 1;118(Pt 19):4495-509
references.pmid: 16179608
references.citation: Mol Cell Biochem. 2009 Apr;324(1-2):139-45
references.pmid: 19107325
references.citation: Heart Vessels. 1998;13(4):199-208
references.pmid: 10442402
references.citation: Pharmacol Ther. 2008 Nov;120(2):172-85
references.pmid: 18786563
references.citation: EMBO J. 2008 Feb 20;27(4):642-53
references.pmid: 18200042
references.citation: Cytokine. 2009 Apr;46(1):137-41
references.pmid: 19223199
references.citation: Arterioscler Thromb Vasc Biol. 2009 May;29(5):754-60
references.pmid: 19213943
references.citation: Expert Opin Ther Targets. 2004 Oct;8(5):409-22
references.pmid: 15469392
references.citation: Int J Oncol. 2000 Dec;17(6):1179-85
references.pmid: 11078803
references.citation: Hypertension. 2000 Jun;35(6):1191-6
references.pmid: 10856262
references.citation: Cardiovasc Res. 2004 Sep 1;63(4):611-6
references.pmid: 15306216
references.citation: Nat Rev Cancer. 2009 Nov;9(11):798-809
references.pmid: 19851315
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12929-34
references.pmid: 14566054
references.citation: Circ Res. 2008 Jan 4;102(1):131-5
references.pmid: 17967780
references.citation: Circulation. 1998 Jul 28;98(4):346-52
references.pmid: 9711940
references.citation: J Mol Cell Cardiol. 2001 Nov;33(11):1929-36
references.pmid: 11708838
references.citation: J Clin Invest. 2005 Mar;115(3):547-55
references.pmid: 15765136
references.citation: J Exp Med. 2003 Nov 17;198(10):1517-25
references.pmid: 14623907
references.citation: Circ Res. 1997 Oct;81(4):611-7
references.pmid: 9314843
references.citation: J Hypertens. 2005 Dec;23(12):2297-304
references.pmid: 16269972
references.citation: Future Cardiol. 2009 Mar;5(2):175-89
references.pmid: 19371191
references.citation: Immunity. 1999 Jan;10(1):105-15
references.pmid: 10023775
references.citation: Cardiovasc Res. 2005 Feb 1;65(2):428-35
references.pmid: 15639482
references.citation: Eur J Cell Biol. 2009 Mar;88(3):153-66
references.pmid: 18996616
references.citation: Circ Res. 2003 Aug 8;93(3):221-9
references.pmid: 12855672
references.citation: Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H1635-44
references.pmid: 11009450
references.citation: Circ Res. 1997 Oct;81(4):627-35
references.pmid: 9314845
references.citation: Oncogene. 2004 Sep 20;23(43):7150-60
references.pmid: 15378075
references.citation: Stem Cells. 2004;22(4):522-30
references.pmid: 15277698
references.citation: Vascul Pharmacol. 2006 Dec;45(6):350-7
references.pmid: 16822720
references.citation: Eur J Heart Fail. 2007 Oct;9(10):1032-7
references.pmid: 17766177
references.citation: Nat Med. 2004 Jan;10(1):55-63
references.pmid: 14702635
references.citation: Science. 2009 Feb 6;323(5915):793-7
references.pmid: 19131594
references.citation: Cardiovasc Res. 2000 Sep;47(4):797-805
references.pmid: 10974228
references.citation: Cell Res. 2008 Feb;18(2):254-67
references.pmid: 18227858
references.citation: Trends Cardiovasc Med. 2000 Oct;10(7):298-303
references.pmid: 11343970
references.citation: Bioessays. 2009 Apr;31(4):370-7
references.pmid: 19274656
references.citation: Int J Cardiol. 2008 Jan 24;123(3):366-8
references.pmid: 17689746
references.citation: Mol Cell Biol. 2005 Sep;25(17):7432-40
references.pmid: 16107692
references.citation: Am J Physiol. 1991 Oct;261(4 Pt 2):H989-95
references.pmid: 1928418
references.citation: Cardiovasc Res. 2008 Oct 1;80(1):69-77
references.pmid: 18567640
references.citation: Oncogene. 2001 Jun 14;20(27):3464-74
references.pmid: 11429693
references.citation: Science. 1994 Jun 3;264(5164):1415-21
references.pmid: 8197455
references.citation: Circulation. 2001 Aug 28;104(9):979-81
references.pmid: 11524388
references.citation: Clin Cancer Res. 2003 Jan;9(1):316-26
references.pmid: 12538484
references.citation: Biochem Biophys Res Commun. 1997 Aug 8;237(1):90-4
references.pmid: 9266835
references.citation: Science. 1977 Jul 8;197(4299):165-7
references.pmid: 877547
references.citation: Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1072-8
references.pmid: 20081106
references.citation: J Clin Invest. 2001 Nov;108(10):1459-67
references.pmid: 11714737
references.citation: Circulation. 1995 Mar 1;91(5):1520-4
references.pmid: 7867193
references.citation: Cell Physiol Biochem. 2008;21(4):305-14
references.pmid: 18441519
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9050-5
references.pmid: 11481471
references.citation: Cardiovasc Res. 2009 Jul 15;83(2):247-61
references.pmid: 19176601
references.citation: Biochem Biophys Res Commun. 1998 Dec 9;253(1):147-50
references.pmid: 9875235
references.citation: Trends Genet. 2004 Jan;20(1):23-32
references.pmid: 14698616
references.citation: Oncogene. 2004 Oct 18;23(48):8017-23
references.pmid: 15489919
references.citation: Gene Expr. 1999;7(4-6):311-9
references.pmid: 10440232
references.citation: Circulation. 2010 Feb 9;121(5):684-91
references.pmid: 20100971
references.citation: Hypertension. 2007 Nov;50(5):977-83
references.pmid: 17846346
references.citation: Nature. 2006 Apr 13;440(7086):944-8
references.pmid: 16612386
references.citation: Am J Cardiol. 2004 Jul 15;94(2):249-51
references.pmid: 15246916
references.citation: J Biol Chem. 2006 Mar 10;281(10):6442-7
references.pmid: 16407199
references.citation: J Mol Cell Cardiol. 2004 Mar;36(3):381-92
references.pmid: 15010277
references.citation: Eur J Clin Invest. 2001 May;31(5):389-97
references.pmid: 11380590
references.citation: Mol Cancer Res. 2009 Nov;7(11):1854-60
references.pmid: 19903771
references.citation: Am J Cardiol. 2006 Jul 1;98(1):14-8
references.pmid: 16784912
references.citation: Circ Res. 1993 Jun;72(6):1293-9
references.pmid: 8495557
references.citation: Circ Res. 2007 Sep 14;101(6):545-59
references.pmid: 17872473
references.citation: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5590-4
references.pmid: 9576927
references.citation: Trends Cell Biol. 2002 Sep;12(9):432-8
references.pmid: 12220864
references.citation: Circulation. 2007 Jul 31;116(5):535-44
references.pmid: 17606840
references.citation: J Immunol. 2008 Feb 15;180(4):2625-33
references.pmid: 18250474
references.citation: Cancer Res. 2001 Jul 1;61(13):5137-44
references.pmid: 11431352
references.citation: Stem Cells. 2005 Apr;23(4):530-43
references.pmid: 15790774
references.citation: Biochem Biophys Res Commun. 2000 Mar 24;269(3):798-802
references.pmid: 10720495
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11307-12
references.pmid: 11027332
references.citation: Cancer Lett. 2006 Jan 8;231(1):12-9
references.pmid: 16356826
references.citation: Cytokine. 2007 Nov;40(2):89-97
references.pmid: 17920926
references.citation: J Mol Cell Cardiol. 2005 Jan;38(1):185-92
references.pmid: 15623435
references.citation: Am Heart J. 2000 Dec;140(6):E28
references.pmid: 11100001
references.citation: Blood. 2002 Jan 1;99(1):102-10
references.pmid: 11756159
references.citation: Nat Rev Cardiol. 2009 Apr;6(4):283-91
references.pmid: 19352332
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1790-800
references.pmid: 16608881
references.citation: Circulation. 2008 Nov 4;118(19):1915-9
references.pmid: 18981312
references.citation: Biochem J. 2003 Aug 15;374(Pt 1):1-20
references.pmid: 12773095
references.citation: Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3801-4
references.pmid: 9108058
references.citation: Cardiovasc Res. 2010 Jan 1;85(1):90-9
references.pmid: 19696070
references.citation: J Biol Chem. 2005 Mar 25;280(12):11528-34
references.pmid: 15649887
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):931-6
references.pmid: 10639182
references.citation: Cell. 2007 Feb 9;128(3):589-600
references.pmid: 17289576
references.citation: Mol Cell Biol. 2004 Oct;24(19):8447-56
references.pmid: 15367666
references.citation: Mol Endocrinol. 2003 Sep;17(9):1815-23
references.pmid: 12791771
references.citation: Int J Cardiol. 2011 Mar 3;147(2):202-8
references.pmid: 19751951
references.citation: FEBS Lett. 2001 Apr 20;495(1-2):71-6
references.pmid: 11322950
references.citation: Stem Cells. 2004;22(5):861-72
references.pmid: 15342949
references.citation: Cell. 1994 Apr 8;77(1):63-71
references.pmid: 7512451
references.citation: Stem Cells Dev. 2010 Jan;19(1):53-60
references.pmid: 19400741
references.citation: Int J Cardiol. 2005 Sep 1;103(3):266-71
references.pmid: 16098388
references.citation: Kobe J Med Sci. 2003;49(1-2):25-37
references.pmid: 12796566
references.citation: Cardiovasc Res. 2006 Sep 1;71(4):684-94
references.pmid: 16828072
references.citation: Mol Cell Biochem. 2000 Sep;212(1-2):171-5
references.pmid: 11108148
references.citation: Basic Res Cardiol. 2007 Sep;102(5):393-411
references.pmid: 17918316
references.citation: Science. 1994 Jan 7;263(5143):89-92
references.pmid: 8272872
references.citation: EMBO J. 2003 Mar 17;22(6):1325-35
references.pmid: 12628925
references.citation: Curr Pharm Des. 2004;10(23):2839-50
references.pmid: 15379672
references.citation: J Clin Invest. 2001 Feb;107(3):351-62
references.pmid: 11160159
references.citation: Science. 2002 May 31;296(5573):1653-5
references.pmid: 12040185
references.citation: Stem Cells. 2004;22(5):770-8
references.pmid: 15342941
references.citation: J Clin Invest. 2010 Jan;120(1):303-14
references.pmid: 20038813
references.citation: J Biol Chem. 2002 Feb 22;277(8):6676-81
references.pmid: 11744720