Aerobic Exercise and Granulocyte Colony-Stimulating Factor Treatment Augment Myocardial Regeneration in Rat with Myocardial Infarction

CAI Meng-xin; ZHANG Juan-juan; SHI Xiu-chao; TIAN Zhen-jun

doi:10.16469/j.css.2013.05.008

China Sport Science > 2013 > 33(5): 50-58,67. > DOI: 10.16469/j.css.2013.05.008

CAI Meng-xin, ZHANG Juan-juan, SHI Xiu-chao, TIAN Zhen-jun. 2013: Aerobic Exercise and Granulocyte Colony-Stimulating Factor Treatment Augment Myocardial Regeneration in Rat with Myocardial Infarction. China Sport Science, 33(5): 50-58,67. DOI: 10.16469/j.css.2013.05.008

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Aerobic Exercise and Granulocyte Colony-Stimulating Factor Treatment Augment Myocardial Regeneration in Rat with Myocardial Infarction

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Received Date: January 29, 2013

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Abstract

Objectives:To discuss the influence and possible mechanism of aerobic exercise(AE) and granulocyte colony-stimulating factor(G-CSF) treatment on myocardial regeneration and improvement of cardiac function in rats with myocardial infarction(MI).Methods:Adult male sprague-dawley rats,weight about 180²20g were randomly divided into:Sham-operated group(Sham),Sedentary MI group(MI),MI with AE group(ME),MI with G-CSF treatment group(MG) and MI with AE plus G-CSF treatment group(MGE).The MI model in rat was established by ligation of the left anterior descending(LAD) coronary artery,and rats in ME and MGE were subjected to 8-week treadmill training.At the end of the 8-week training,hemodynamic measurement was performed to evaluate cardiac function;hearts were picked for TTC dyeing and histological section;the expression levels of factors related to cell proliferation and stem cell homing were detected by immunohistochemical measurement,western blot or RT-PCR.Results:Compared to Sham,the MI rats were found to have impaired cardiac function and increased cardiac fibrosis,the expression levels of PCNA,Ki-67 and VLA-4 increased(P<0.01),and mRNA and protein levels of GATA4 decreased(P<0.01,P<0.05);compared to MI rats,AE or G-CSF treatment ameliorated cardiac remodeling,improved cardiac function,decreased infarct size(P<0.05),and increased the expression of PCNA,Ki-67,c-kit,CD29,CXCR4,VLA-4 in ME and MG rats;the combined treatment had a better effect than pure intervention factors.Conclusion:AE or G-CSF treatment significantly improved myocardial remodeling and cardiac function in MI rats,and increased myocardial cells regeneration and activation of the stem cell movement.The better effects were appeared with the combined treatment.
- aerobic exercise,
- myocardial infarction,
- granulocyte colony-stimulating factor,
- stem cell,
- cardiomyocyte proliferation,
- rat,
- animal experiment

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References (54)

References

陈运贤,欧瑞明,钟雪云,等.粒细胞集落刺激因子动员骨髓干细胞治疗大鼠急性心肌梗塞[J].中国病理生理杂志,2002,18(1):1-3.

田振军,蔡梦昕,邢维新.有氧运动对心肌细胞增殖/凋亡的影响及其机制探讨[J].体育科学,2012,32(3):60-66.

ABBOTT JD,HUANG Y,LIU D,et al.Stromal cell-derived fac-tor-1alpha plays a critical role in stem cell recruitment to theheart after myocardial infarction but is not sufficient to inducehoming in the absence of injury[J].Circulation,2004,110(21):3300-3305.

ARMINAN A,GANDIA C,BARTUAL M,et al.Cardiac differ-entiation is driven by NKX2.5and GATA4nuclear translocationin tissue-specific mesenchymal stem cells[J].Stem Cells Dev,2009,18(6):907-918.

ASKARI AT,UNZEK S,POPOVIC ZB,et al.Effect of stromal-cell-derived factor 1on stem-cell homing and tissue regenerationin ischaemic cardiomyopathy[J].Lancet,2003,362(9385):697-703.

BELARDINELLI R,FACCENDA E,VOLPE L,et al.Exercisetraining as a form of cardiovascular therapy in chronic heart fail-ure[J].Ital Heart J,2000,1(10):653-655.

BELTRAMI A P,BARLUCCHI L,TORELLA D,et al.Adultcardiac stem cells are multipotent and support myocardial regen-eration[J].Cell,2003,114(6):763-776.

BELTRAMI AP,URBANEK K,KAJSTURA J,et al.Evidencethat human cardiac myocytes divide after myocardial infarction[J].N Engl J Med,2001,344(23):1750-1757.

BERGMANN O,BHARDWAJ RD,BERNARD S,et al.Evi-dence for cardiomyocyte renewal in humans[J].Science,2009,324(5923):98-102.

BERSELL K,ARAB S,HARING B,et al.Neuregulin1/ErbB4signaling induces cardiomyocyte proliferation and repair ofheart injury[J].Cell,2009,138(2):257-270.

BOSTROM P,MANN N,WU J,et al.C/EBPbeta controls ex-ercise-induced cardiac growth and protects against pathologicalcardiac remodeling[J].Cell,2010,143(7):1072-1083.

DOMINICI M,Le BLANC K,MUELLER I,et al.Minimal cri-teria for defining multipotent mesenchymal stromal cells.TheInternational Society for Cellular Therapy position statement[J].Cytotherapy,2006,8(4):315-317.

DUBACH P,MYERS J,DZIEKAN G,et al.Effect of exercisetraining on myocardial remodeling in patients with reduced leftventricular function after myocardial infarction:application ofmagnetic resonance imaging[J].Circulation,1997,95(8):2060-2067.

ELLISON GM,WARING CD,VICINANZA C,et al.Physio-logical cardiac remodeling in response to endurance exercisetraining:cellular and molecular mechanisms[J].Heart,2012,98(1):5-10.

FRENCH J P,HAMILTON K L,QUINDRY J C,et al.Exer-cise-induced protection against myocardial apoptosis and necro-sis:MnSOD,calcium-handling proteins,and calpain[J].FasebJ,2008,22(8):2862-2871.

FUKUHARA S,TOMITA S,NAKATANI T,et al.G-CSFpromotes bone marrow cells to migrate into infarcted miceheart,and differentiate into cardiomyocytes[J].Cell Trans-plant,2004,13(7-8):741-748.

GIANNUZZI P,TEMPORELLI P L,CORRA U,et al.Attenu-ation of unfavorable remodeling by exercise training in postin-farction patients with left ventricular dysfunction:results of theexercise in left ventricular dysfunction(ELVD)trial[J].Circu-lation,1997,96(6):1790-1797.

HAMAMOTO M,TOMITA S,NAKATANI T,et al.Granulo-cyte-colony stimulating factor directly enhances proliferation ofhuman troponin I-positive cells derived from idiopathic dilatedcardiomyopathy through specific receptors[J].J Heart LungTransplant,2004,23(12):1430-1437.

HARADA M,QIN Y,TAKANO H,et al.G-CSF prevents car-diac remodeling after myocardial infarction by activating theJak-Stat pathway in cardiomyocytes[J].Nat Med,2005,11(3):305-311.

HAYKOWSKY M,SCOTT J,ESCH B,et al.A meta-analysisof the effects of exercise training on left ventricular remodelingfollowing myocardial infarction:start early and go longer forgreatest exercise benefits on remodeling[J].Trials,2011,12:92.

KAJSTURA J,LERI A,FINATO N,et al.Myocyte prolifera-tion in end-stage cardiac failure in humans[J].Proc Natl AcadSci USA,1998,95(15):8801-8805.

KAJSTURA J,URBANEK K,PERL S,et al.Cardiomyogene-sis in the adult human heart[J].Circ Res,2010,107(2):305-315.

KANELLAKIS P,SLATER NJ,Du XJ,et al.Granulocyte col-ony-stimulating factor and stem cell factor improve endogenousrepair after myocardial infarction[J].Cardiovasc Res,2006,70(1):117-125.

KORZENIOWSKA-KUBACKA I,BILINSKA M,MICHA-LAK E,et al.Influence of exercise training on left ventriculardiastolic function and its relationship to exercise capacity inpatients after myocardial infarction[J].Cardiol J,2010,17(2):136-142.

KUHN B,DEL MF,HAJJAR RJ,et al.Periostin induces pro-liferation of differentiated cardiomyocytes and promotes cardiacrepair[J].Nat Med,2007,13(8):962-969.

LAFLAMME MA,MURRY CE.Regenerating the heart[J].Nat Biotechnol,2005,23(7):845-856.

LAPIDOT T,DAR A,KOLLET O.How do stem cells findtheir way home?[J].Blood,2005,106(6):1901-1910.

LIMANA F,BERTOLAMI C,MANGONI A,et al.Myocardialinfarction induces embryonic reprogramming of epicardial c-kit(+)cells:role of the pericardial fluid[J].J Mol Cell Cardiol,2010,48(4):609-618.

LINKE A,MULLER P,NURZYNSKA D,et al.Stem cells inthe dog heart are self-renewing,clonogenic,and multipotent andregenerate infarcted myocardium,improving cardiac function[J].Proc Natl Acad Sci USA,2005,102(25):8966-8971.

MINATOGUCHI S,TAKEMURA G,CHEN XH,et al.Accel-eration of the healing process and myocardial regeneration maybe important as a mechanism of improvement of cardiac func-tion and remodeling by postinfarction granulocyte colony-stim-ulating factor treatment[J].Circulation,2004,109(21):2572-2580.

MORIMOTO H,TAKAHASHI M,SHIBA Y,et al.Bone mar-row-derived CXCR4+cells mobilized by macrophage colony-stimulating factor participate in the reduction of infarct areaand improvement of cardiac remodeling after myocardial infarc-tion in mice[J].Am J Pathol,2007,171(3):755-766.

NIENABER C A,PETZSCH M,KLEINE H D,et al.Effects ofgranulocyte-colony-stimulating factor on mobilization of bone-marrow-derived stem cells after myocardial infarction in hu-mans[J].Nat Clin Pract Cardiovasc Med,2006,3Suppl 1(S73-S77).

ORLIC D,KAJSTURA J,CHIMENTI S,et al.Bone marrowcells regenerate infarcted myocardium[J].Nature,2001,410(6829):701-705.

ORLIC D,KAJSTURA J,CHIMENTI S,et al.Mobilized bonemarrow cells repair the infarcted heart,improving function andsurvival[J].Proc Natl Acad Sci USA,2001,98(18):10344-10349.

PFEFFER MA,BRAUNWALD E.Ventricular remodeling af-ter myocardial infarction Experimental observations and clinicalimplications[J].Circulation,1990,81(4):1161-1172.

PORRELLO ER,MAHMOUD AI,SIMPSON E,et al.Transi-ent regenerative potential of the neonatal mouse heart[J].Sci-ence,2011,331(6020):1078-1080.

RUVINOV E,LEOR J,COHEN S.The promotion of myocar-dial repair by the sequential delivery of IGF-1and HGF from aninjectable alginate biomaterial in a model of acute myocardialinfarction[J].Biomaterials,2011,32(2):565-578.

SENYO S E,STEINHAUSER M L,PIZZIMENTI C L,et al.Mammalian heart renewal by pre-existing cardiomyocytes[J].Nature,2012,493(7432):433-436.

SHEPHARD R J,BALADY G J.Exercise as cardiovasculartherapy[J].Circulation,1999,99(7):963-972.

SMART N,RILEY P R.The stem cell movement[J].Circ Res,2008,102(10):1155-1168.

SOONPAA M H,FIELD L J.Survey of studies examiningmammalian cardiomyocyte DNA synthesis[J].Circ Res,1998,83(1):15-26.

SWYNGHEDAUW B.Molecular mechanisms of myocardial re-modeling[J].Physiol Rev,1999,79(1):215-262.

TAMAMORI-ADACHI M,TAKAGI H,HASHIMOTO K,etal.Cardiomyocyte proliferation and protection against post-my-ocardial infarction heart failure by cyclin D1and Skp2ubiquitinligase[J].Cardiovasc Res,2008,80(2):181-190.

TAO Z,CHEN B,TAN X,et al.Coexpression of VEGF andangiopoietin-1promotes angiogenesis and cardiomyocyte prolif-eration reduces apoptosis in porcine myocardial infarction(MI)heart[J].Proc Natl Acad Sci USA,2011,108(5):2064-2069.

THOMPSON P D,BUCHNER D,PINA I L,et al.Exercise andphysical activity in the prevention and treatment of atheroscle-rotic cardiovascular disease:a statement from the Council onClinical Cardiology(Subcommittee on Exercise,Rehabilitation,and Prevention)and the Council on Nutrition,Physical Activi-ty,and Metabolism(Subcommittee on Physical Activity)[J].Circulation,2003,107(24):3109-3116.

URBANEK K,TORELLA D,SHEIKH F,et al.Myocardialregeneration by activation of multipotent cardiac stem cells inischemic heart failure[J].Proc Natl Acad Sci USA,2005,102(24):8692-8697.

WAHL P,BRIXIUS K,BLOCH W.Exercise-induced stem cellactivation and its implication for cardiovascular and skeletalmuscle regeneration[J].Minim Invasive Ther Allied Technol,2008,17(2):91-99.

WARD M R,STEWART D J,KUTRYK M J.Endothelial pro-genitor cell therapy for the treatment of coronary disease,acuteMI,and pulmonary arterial hypertension:current perspectives[J].Catheter Cardiovasc Interv,2007,70(7):983-998.

WARING CD,VICINANZA C,PAPALAMPROU A,et al.The adult heart responds to increased workload with physio-logic hypertrophy,cardiac stem cell activation,and new myo-cyte formation[EB/OL].Eur Heart J,2012,DOI: 10.1093/eu-rheartj/ehs338.

WOJAKOWSKI W,TENDERA M,MICHALOWSKA A,etal.Mobilization of CD34/CXCR4+,CD34/CD117+,c-met+stem cells,and mononuclear cells expressing early cardiac,muscle,and endothelial markers into peripheral blood in pa-tients with acute myocardial infarction[J].Circulation,2004,110(20):3213-3220.

WOULFE K C,GAO E,LAL H,et al.Glycogen synthase ki-nase-3beta regulates post-myocardial infarction remodeling andstress-induced cardiomyocyte proliferation in vivo[J].Circ Res,2010,106(10):1635-1645.

XU X,WAN W,POWERS AS,et al.Effects of exercise train-ing on cardiac function and myocardial remodeling in post myo-cardial infarction rats[J].J Mol Cell Cardiol,2008,44(1):114-122.

XU X,ZHAO W,WAN W,et al.Exercise training combinedwith angiotensin II receptor blockade reduces oxidative stressafter myocardial infarction in rats[J].Exp Physiol,2010,95(10):1008-1015.

ZHANG Y,LI TS,LEE ST,et al.Dedifferentiation and prolif-eration of mammalian cardiomyocytes[J].PLoS One,2010,5(9):e12559.

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