title: Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats.
abstract: BACKGROUND
  Gαq protein carboxyl terminus imitation polypeptide (GCIP)-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin.
  
  
  RESULTS
  Forty-eight rats were randomly divided into the following six groups receiving vehicle (control), doxorubicin (Dox), losartan (6 mg/kg, i.g.) and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid), respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg) significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg) could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC), Bcl-2, protein kinase C (PKC) ε and phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L) decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.
  
  
  CONCLUSIONS
  GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing 400038, China; Department of Clinical Laboratory, First Affiliated Hospital of North Sichuan Medical College, Sichuan Nanchong 637000, China.
authors.forename: Xiao Lan
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yang Fei
authors.initials: YF
authors.lastname: Tong
authors.affiliation: Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 40038, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Ya Li
authors.initials: YL
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of North Sichuan Medical College, Sichuan Nanchong 637000, China.
authors.forename: Guo Yuan
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica and Department of Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing 40038, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Pharmacology, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hai-Gang
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D006334:Heart Function Tests; D007150:Immunohistochemistry; D051379:Mice; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects*; D019210:Troponin I / Q000097:blood
chemical_list: D017931:DNA Primers; C572754:GCIP-27 peptide; C584019:Myh6 protein, mouse; D010455:Peptides; D019210:Troponin I; D004317:Doxorubicin; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases
references.citation: Circulation. 1989 Sep;80(3):551-63
references.pmid: 2548768
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10140-5
references.pmid: 9707614
references.citation: J Biol Chem. 2013 May 31;288(22):15745-59
references.pmid: 23589292
references.citation: PLoS One. 2012;7(7):e41691
references.pmid: 22848568
references.citation: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1438-46
references.pmid: 21765056
references.citation: Hypertension. 2001 Sep;38(3 Pt 2):576-80
references.pmid: 11566934
references.citation: J Mol Cell Cardiol. 1996 Dec;28(12):2467-77
references.pmid: 9004163
references.citation: Circulation. 2003 Feb 25;107(7):984-91
references.pmid: 12600911
references.citation: J Am Coll Cardiol. 2009 Apr 14;53(15):e1-e90
references.pmid: 19358937
references.citation: Eur J Clin Invest. 2004 Feb;34(2):85-93
references.pmid: 14764070
references.citation: Nutrition. 2000 Oct;16(10):837-42
references.pmid: 11054588
references.citation: N Engl J Med. 2007 Mar 15;356(11):1140-51
references.pmid: 17360992
references.citation: J Cardiovasc Med (Hagerstown). 2011 Oct;12(10):732-5
references.pmid: 21873882
references.citation: Clin Physiol. 2001 Nov;21(6):661-72
references.pmid: 11722473
references.citation: Ann Oncol. 2000 Sep;11(9):1121-6
references.pmid: 11061605
references.citation: Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2169-81
references.pmid: 19801496
references.citation: Eur Heart J. 2012 Jul;33(14):1787-847
references.pmid: 22611136
references.citation: Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9320-5
references.pmid: 9256480
references.citation: Biochim Biophys Acta. 2005 Jun 10;1740(3):499-513
references.pmid: 15949720
references.citation: Nature. 2010 Jul 1;466(7302):62-7
references.pmid: 20596014
references.citation: Circ Res. 2014 Jan 31;114(3):565-71
references.pmid: 24481846
references.citation: Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2777-89
references.pmid: 15271671
references.citation: Am J Med. 2001 May 7;110 Suppl 7A:37S-46S
references.pmid: 11334774
references.citation: Cardiovasc Drugs Ther. 1997 Jan;10(6):717-25
references.pmid: 9110115
references.citation: PLoS One. 2014;9(3):e91074
references.pmid: 24646838
references.citation: J Mol Cell Cardiol. 2011 Mar;50(3):460-70
references.pmid: 21111744
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8121-6
references.pmid: 9223325
references.citation: BMJ Open. 2012 Mar 26;2(2):e000787
references.pmid: 22454188
references.citation: Mol Med. 2011 Mar-Apr;17(3-4):201-10
references.pmid: 21152695
references.citation: J Biol Chem. 2004 Jan 30;279(5):3596-604
references.pmid: 14600145
references.citation: Int J Cardiol. 2013 Jan 20;162(3):199-209
references.pmid: 22000973
references.citation: Circulation. 2005 Jul 5;112(1):54-9
references.pmid: 15998695
references.citation: Phys Ther. 1996 May;76(5):516-33
references.pmid: 8637939
references.citation: J Cell Biol. 2002 Mar 4;156(5):905-19
references.pmid: 11864993
references.citation: Circ Res. 1994 Apr;74(4):555-64
references.pmid: 8137493
references.citation: Circulation. 2007 Sep 18;116(12):1413-23
references.pmid: 17875982
references.citation: Circ Res. 1995 Oct;77(4):759-64
references.pmid: 7554123
references.citation: Am J Physiol Heart Circ Physiol. 2014 Oct 1;307(7):H987-95
references.pmid: 25108013
references.citation: Am J Physiol Heart Circ Physiol. 2003 Apr;284(4):H1043-7
references.pmid: 12666659
references.citation: J Clin Invest. 1992 Nov;90(5):2022-30
references.pmid: 1331179
references.citation: Am J Physiol. 1996 Sep;271(3 Pt 2):H1031-9
references.pmid: 8853338
references.citation: Congest Heart Fail. 2011 Jan-Feb;17(1):49
references.pmid: 21272230
references.citation: J Mol Cell Cardiol. 2014 Nov;76:116-25
references.pmid: 25169970
references.citation: Can J Physiol Pharmacol. 2012 May;90(5):627-35
references.pmid: 22550975
references.citation: J Pharmacol Exp Ther. 2002 Mar;300(3):862-7
references.pmid: 11861791
references.citation: Mol Cell Biochem. 2000 Apr;207(1-2):77-86
references.pmid: 10888230
references.citation: Braz J Med Biol Res. 2000 Dec;33(12):1491-6
references.pmid: 11105103
references.citation: Biol Pharm Bull. 2009 Mar;32(3):376-81
references.pmid: 19252281
references.citation: J Mol Cell Cardiol. 2005 Jan;38(1):47-62
references.pmid: 15623421
references.citation: Biol Pharm Bull. 2011;34(10):1527-32
references.pmid: 21963491
references.citation: Diabetes. 2013 Jul;62(7):2318-28
references.pmid: 23474486
references.citation: Ann Agric Environ Med. 2011 Dec;18(2):194-202
references.pmid: 22324071
references.citation: Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1215-21
references.pmid: 18518877
references.citation: Anesthesiology. 2009 Jul;111(1):209; author reply 209-10
references.pmid: 19546703
references.citation: Ann Agric Environ Med. 2011 Dec;18(2):260-4
references.pmid: 22216793
references.citation: Biomed Res Int. 2014;2014:802539
references.pmid: 24719888
references.citation: Eur J Heart Fail. 2014 Mar;16(3):317-24
references.pmid: 24464640
references.citation: Eur J Pharm Sci. 2013 Aug 16;49(5):791-9
references.pmid: 23748000
references.citation: Ultrasound Med Biol. 2008 Feb;34(2):208-14
references.pmid: 17935867
references.citation: Clin Exp Pharmacol Physiol. 2007 Dec;34(12):1276-81
references.pmid: 17973867
references.citation: J Biol Chem. 1990 Mar 15;265(8):4302-8
references.pmid: 2155221
references.citation: Am J Physiol Heart Circ Physiol. 2001 Dec;281(6):H2500-10
references.pmid: 11709417