Abstract
Heart failure is a life-threatening disorder associated with the loss of cardiomyocytes. The heart has some endogenous although limited regenerative capacity, thus enhancing cardiac regeneration or stimulating endogenous repair mechanism after cardiac injury is of great interest. The benefits of exercise in heart diseases have been recognized for centuries. Besides the promotion of a favorable cardiac function, exercise is also associated with new cardiomyocytes formation. Exercise may lead to cardiomyocytes renewal from pre-existing cardiomyocytes proliferation or cardiac stem/progenitor cells differentiation. A deep understanding of exercise-induced formation of new cardiomyocytes will enable us to develop novel therapeutics for heart diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Madonna R, Van Laake LW, Davidson SM et al (2016) Position paper of the European Society of Cardiology Working Group Cellular Biology of the heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure. Eur Heart J 37(23):1789–1798
Maracy MR, Isfahani MT, Kelishadi R et al (2015) Burden of ischemic heart diseases in Iran, 1990-2010: findings from the global burden of disease study 2010. J Res Med Sci 20(11):1077–1083
Kikuchi K, Poss KD (2012) Cardiac regenerative capacity and mechanisms. Annu Rev Cell Dev Biol 28:719–741
Murry CE, Reinecke H, Pabon LM (2006) Regeneration gaps: observations on stem cells and cardiac repair. J Am Coll Cardiol 47(9):1777–1785
Palojoki E, Saraste A, Eriksson A et al (2001) Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats. Am J Physiol Heart Circ Physiol 280(6):H2726–H2731
van den Borne SW, Diez J, Blankesteijn WM et al (2010) Myocardial remodeling after infarction: the role of myofibroblasts. Nat Rev Cardiol 7(1):30–37
Barandon L, Couffinhal T, Dufourcq P et al (2004) Study of postmyocardial infarction scar-formation mechanisms: advantage of an experimental myocardial infarction model in mice. Can J Cardiol 20(14):1467–1475
Mill JG, Stefanon I, dos Santos L et al (2011) Remodeling in the ischemic heart: the stepwise progression for heart failure. Braz J Med Biol Res 44(9):890–898
Lin Z, Pu WT (2014) Strategies for cardiac regeneration and repair. Sci Transl Med 6(239):239rv231
Powers SK, Lennon SL, Quindry J et al (2002) Exercise and cardioprotection. Curr Opin Cardiol 17(5):495–502
Golbidi S, Laher I (2011) Molecular mechanisms in exercise-induced cardioprotection. Cardiol Res Pract 2011:972807
Powers SK, Smuder AJ, Kavazis AN et al (2014) Mechanisms of exercise-induced cardioprotection. Physiology (Bethesda) 29(1):27–38
Erokhina IL, Rumyantsev PP (1986) Ultrastructure of DNA-synthesizing and mitotically dividing myocytes in sinoatrial node of mouse embryonal heart. J Mol Cell Cardiol 18(12):1219–1231
Zak R (1974) Development and proliferative capacity of cardiac muscle cells. Circ Res 35(2 Suppl II):17–26
Laflamme MA, Murry CE (2011) Heart regeneration. Nature 473(7347):326–335
Leu M, Ehler E, Perriard JC (2001) Characterisation of postnatal growth of the murine heart. Anat Embryol (Berl) 204(3):217–224
Hirschy A, Schatzmann F, Ehler E et al (2006) Establishment of cardiac cytoarchitecture in the developing mouse heart. Dev Biol 289(2):430–441
Lopaschuk GD, Collins-Nakai RL, Itoi T (1992) Developmental changes in energy substrate use by the heart. Cardiovasc Res 26(12):1172–1180
Bloomekatz J, Galvez-Santisteban M, Chi NC (2016) Myocardial plasticity: cardiac development, regeneration and disease. Curr Opin Genet Dev 40:120–130
Ahuja P, Sdek P, MacLellan WR (2007) Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol Rev 87(2):521–544
Olivetti G, Abbi R, Quaini F et al (1997) Apoptosis in the failing human heart. N Engl J Med 336(16):1131–1141
Kajstura J, Leri A, Finato N et al (1998) Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci U S A 95(15):8801–8805
Beltrami AP, Urbanek K, Kajstura J et al (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 344(23):1750–1757
Kajstura J, Urbanek K, Perl S et al (2010) Cardiomyogenesis in the adult human heart. Circ Res 107(2):305–315
Soonpaa MH, Field LJ (1997) Assessment of cardiomyocyte DNA synthesis in normal and injured adult mouse hearts. Am J Phys 272(1 Pt 2):H220–H226
Hsieh PC, Segers VF, Davis ME et al (2007) Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 13(8):970–974
Bergmann O, Bhardwaj RD, Bernard S et al (2009) Evidence for cardiomyocyte renewal in humans. Science 324(5923):98–102
Senyo SE, Steinhauser ML, Pizzimenti CL et al (2013) Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493(7432):433–436
Bersell K, Arab S, Haring B et al (2009) Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell 138(2):257–270
Soonpaa MH, Rubart M, Field LJ (2013) Challenges measuring cardiomyocyte renewal. Biochim Biophys Acta 1833(4):799–803
Bearzi C, Rota M, Hosoda T et al (2007) Human cardiac stem cells. Proc Natl Acad Sci U S A 104(35):14068–14073
Urbanek K, Cesselli D, Rota M et al (2006) Stem cell niches in the adult mouse heart. Proc Natl Acad Sci U S A 103(24):9226–9231
Fuchs E, Horsley V (2011) Ferreting out stem cells from their niches. Nat Cell Biol 13(5):513–518
Lo Celso C, Scadden DT (2011) The haematopoietic stem cell niche at a glance. J Cell Sci 124(Pt 21):3529–3535
Anversa P, Kajstura J, Rota M et al (2013) Regenerating new heart with stem cells. J Clin Invest 123(1):62–70
Oh H, Bradfute SB, Gallardo TD et al (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci U S A 100(21):12313–12318
Smith RR, Barile L, Cho HC et al (2007) Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation 115(7):896–908
Matsuura K, Honda A, Nagai T et al (2009) Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. J Clin Invest 119(8):2204–2217
Bu L, Jiang X, Martin-Puig S et al (2009) Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 460(7251):113–117
Santini MP, Forte E, Harvey RP et al (2016) Developmental origin and lineage plasticity of endogenous cardiac stem cells. Development 143(8):1242–1258
Beltrami AP, Barlucchi L, Torella D et al (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114(6):763–776
Kocher AA, Schlechta B, Gasparovicova A et al (2007) Stem cells and cardiac regeneration. Transpl Int 20(9):731–746
Mathur A, Martin JF (2004) Stem cells and repair of the heart. Lancet 364(9429):183–192
Olson LE, Soriano P (2009) Increased PDGFRalpha activation disrupts connective tissue development and drives systemic fibrosis. Dev Cell 16(2):303–313
Cai CL, Liang X, Shi Y et al (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 5(6):877–889
Torella D, Ellison GM, Nadal-Ginard B et al (2005) Cardiac stem and progenitor cell biology for regenerative medicine. Trends Cardiovasc Med 15(6):229–236
Ellison GM, Galuppo V, Vicinanza C et al (2010) Cardiac stem and progenitor cell identification: different markers for the same cell? Front Biosci (Schol Ed) 2:641–652
Kajstura J, Gurusamy N, Ogorek B et al (2010) Myocyte turnover in the aging human heart. Circ Res 107(11):1374–1386
Gonzalez A, Rota M, Nurzynska D et al (2008) Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res 102(5):597–606
Urbanek K, Torella D, Sheikh F et al (2005) Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A 102(24):8692–8697
Urbanek K, Quaini F, Tasca G et al (2003) Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci U S A 100(18):10440–10445
Steinhauser ML, Lee RT (2011) Regeneration of the heart. EMBO Mol Med 3(12):701–712
Li F, Wang X, Bunger PC et al (1997) Formation of binucleated cardiac myocytes in rat heart: I. Role of actin-myosin contractile ring. J Mol Cell Cardiol 29(6):1541–1551
Li F, Wang X, Gerdes AM (1997) Formation of binucleated cardiac myocytes in rat heart: II. Cytoskeletal organisation. J Mol Cell Cardiol 29(6):1553–1565
Mollova M, Bersell K, Walsh S et al (2013) Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci U S A 110(4):1446–1451
Malliaras K, Terrovitis J (2013) Cardiomyocyte proliferation vs progenitor cells in myocardial regeneration: the debate continues. Glob Cardiol Sci Pract 2013(3):303–315
Ali SR, Hippenmeyer S, Saadat LV et al (2014) Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice. Proc Natl Acad Sci U S A 111(24):8850–8855
Chimenti C, Kajstura J, Torella D et al (2003) Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res 93(7):604–613
Wahl P, Brixius K, Bloch W (2008) Exercise-induced stem cell activation and its implication for cardiovascular and skeletal muscle regeneration. Minim Invasive Ther Allied Technol 17(2):91–99
Bei Y, Zhou Q, Sun Q et al (2015) Exercise as a platform for pharmacotherapy development in cardiac diseases. Curr Pharm Des 21(30):4409–4416
Waring CD, Vicinanza C, Papalamprou A et al (2014) The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J 35(39):2722–2731
Xiao J, Xu T, Li J et al (2014) Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells. Int J Clin Exp Pathol 7(2):663–669
Bostrom P, Mann N, Wu J et al (2010) C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell 143(7):1072–1083
Bezzerides VJ, Platt C, Lerchenmuller C et al (2016) CITED4 induces physiologic hypertrophy and promotes functional recovery after ischemic injury. JCI Insight 1(9)
Liu X, Xiao J, Zhu H et al (2015) miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell Metab 21(4):584–595
Shi J, Bei Y, Kong X et al (2017) miR-17-3p contributes to exercise-induced cardiac growth and protects against myocardial ischemia-reperfusion injury. Theranostics 7(3):664–676
Weeks KL, McMullen JR (2011) The athlete’s heart vs. the failing heart: can signaling explain the two distinct outcomes? Physiology (Bethesda) 26(2):97–105
Ellison GM, Waring CD, Vicinanza C et al (2012) Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms. Heart 98(1):5–10
Kwak HB (2013) Aging, exercise, and extracellular matrix in the heart. J Exerc Rehabil 9(3):338–347
Schuler G, Adams V, Goto Y (2013) Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J 34(24):1790–1799
Sheikh N, Sharma S (2014) Impact of ethnicity on cardiac adaptation to exercise. Nat Rev Cardiol 11(4):198–217
Metkus TS Jr, Baughman KL, Thompson PD (2010) Exercise prescription and primary prevention of cardiovascular disease. Circulation 121(23):2601–2604
Hu G, Barengo NC, Tuomilehto J et al (2004) Relationship of physical activity and body mass index to the risk of hypertension: a prospective study in Finland. Hypertension 43(1):25–30
Kriska AM, Saremi A, Hanson RL et al (2003) Physical activity, obesity, and the incidence of type 2 diabetes in a high-risk population. Am J Epidemiol 158(7):669–675
Rennie KL, McCarthy N, Yazdgerdi S et al (2003) Association of the metabolic syndrome with both vigorous and moderate physical activity. Int J Epidemiol 32(4):600–606
Benton JG, Rusk HA (1954) The relation of physical activity and occupation to coronary artery heart disease. Ann Intern Med 41(5):910–917
Pina IL, Apstein CS, Balady GJ et al (2003) Exercise and heart failure: a statement from the American Heart Association Committee on exercise, rehabilitation, and prevention. Circulation 107(8):1210–1225
Lee DC, Artero EG, Sui X et al (2010) Mortality trends in the general population: the importance of cardiorespiratory fitness. J Psychopharmacol 24(4 Suppl):27–35
O’Connor CM, Whellan DJ, Lee KL et al (2009) Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 301(14):1439–1450
Crimi E, Ignarro LJ, Cacciatore F et al (2009) Mechanisms by which exercise training benefits patients with heart failure. Nat Rev Cardiol 6(4):292–300
Bei Y, Fu S, Chen X, et al (2017) Cardiac cell proliferation is not necessary for exercise-induced cardiac growth but required for its protection against ischaemia/reperfusion injury. J Cell Mol Med
Senyo SE, Lee RT, Kuhn B (2014) Cardiac regeneration based on mechanisms of cardiomyocyte proliferation and differentiation. Stem Cell Res 13(3 Pt B):532–541
Rosenzweig A (2012) Medicine. Cardiac regeneration. Science 338(6114):1549–1550
Sharma S, Merghani A, Mont L (2015) Exercise and the heart: the good, the bad, and the ugly. Eur Heart J 36(23):1445–1453
Acknowledgements
This work was supported by the grants from National Natural Science Foundation of China (81570362, 91639101 and 81200169 to JJ Xiao and 81400647 to Y Bei), and the development fund for Shanghai talents (to JJ Xiao), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042), the grant from Science and Technology Commission of Shanghai Municipality (17010500100).
Competing Financial Interests
The authors declare no competing financial interests.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Shen, L., Wang, H., Bei, Y., Cretoiu, D., Cretoiu, S.M., Xiao, J. (2017). Formation of New Cardiomyocytes in Exercise. In: Xiao, J. (eds) Exercise for Cardiovascular Disease Prevention and Treatment. Advances in Experimental Medicine and Biology, vol 999. Springer, Singapore. https://doi.org/10.1007/978-981-10-4307-9_6
Download citation
DOI: https://doi.org/10.1007/978-981-10-4307-9_6
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-4306-2
Online ISBN: 978-981-10-4307-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)