General Review Article

心肌细胞周期在心脏再生中的作用

卷 20, 期 2, 2019

页: [241 - 254] 页: 14

弟呕挨: 10.2174/1389450119666180801122551

价格: $65

摘要

成年哺乳动物心肌细胞(CMS)具有有限的增殖能力,细胞周期活动导致DNA含量增加,但有丝分裂和胞质分裂是少见的。这使得心脏在替换新形成的心肌细胞时效率很低,就像心肌梗塞和扩张型心肌病等疾病一样,失去了收缩细胞。以不同来源的干细胞植入为基础的再生治疗不能保证新生细胞与常驻细胞的植入和机电连接,这是恢复心脏合胞生理的基本条件。因此,在调控CM细胞周期中发挥相关作用的因素越来越受到人们的关注,以诱导驻留心肌细胞分化为子代细胞,从而在维持生理合胞性能的前提下实现心肌再生。尽管在过去的几十年里取得了科学的进步,但许多问题仍然没有答案,包括在妊娠期和新生儿期心脏发育过程中心肌细胞的增殖是如何被调控的。这可以揭示未知的细胞周期调节机制和分子,这些分子可能被操纵以实现心脏的自我再生。我们在此修订有关CM细胞周期调控的最新数据,最近与细胞周期相关的参与分子和途径,以及涉及它们的实验治疗。

关键词: 细胞周期,心肌细胞,心脏,有丝分裂,INK 4,Cip/Kip。

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[1]
Sharma A, Zhang Y, Wu SM. Harnessing the induction of cardiomyocyte proliferation for cardiac regenerative medicine. Curr Treat Options Cardiovasc Med 2015; 17(10): 404.
[2]
Zebrowski DC, Becker R, Engel FB. Towards regenerating the mammalian heart: Challenges in evaluating experimentally induced adult mammalian cardiomyocyte proliferation. Am J Physiol Heart Circ Physiol 2016; 310(9): H1045-54.
[3]
Laflamme MA, Murry CE. Heart regeneration. Nature 2011; 473(7347): 326-35.
[4]
Bergmann O, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte renewal in humans. Science 2009; 324(5923): 98-102.
[5]
Bergmann O, Zdunek S, Felker A, et al. Dynamics of cell generation and turnover in the human heart. Cell 2015; 161: 1566-75.
[6]
Kajstura J, Urbanek K, Perl S, et al. Cardiomyogenesis in the adult human heart. Circ Res 2010; 107: 305-15.
[7]
Mollova M, Bersell K, Walsh S, et al. Cardiomyocyte proliferation contributes to heart growth in young humans. Proc Natl Acad Sci USA 2013; 110(4): 1446-51.
[8]
Naqvi N, Li M, Calvert JW, et al. A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell 2014; 157(4): 795-807.
[9]
Sharma A, Wu SM. Members only: hypoxia-induced cell-cycle activation in cardiomyocytes. Cell Metab 2015; 22(3): 365-6.
[10]
Siddiqi S, Sussman MA. The heart: mostly postmitotic or mostly premitotic? myocyte cell cycle, senescence, and quiescence. Canadian Journal of Cardiology 2014; 30(11): 1270-8.
[11]
Soonpaa MH, Kim KK, Pajak L, et al. Cardiomyocyte DNA synthesis and binucleation during murine development. Am J Physiol 1996; 271(5Pt2): H2183-9.
[12]
Aguirre A, Montserrat N, Zacchigna S, et al. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell 2014; 15(5): 589-604.
[13]
Alkass K, Panula J, Westman M, et al. No evidence for cardiomyocyte number expansion in preadolescent mice. Cell 2015; 163(4): 1026-36.
[14]
Li F, Wang X, Capasso JM, et al. Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 1996; 28(8): 1737-46.
[15]
Walsh S, Pontén A, Fleischmann BK, et al. Cardiomyocyte cell cycle control and growth estimation in vivo-An analysis based on cardiomyocyte nuclei. Cardiovasc Res 2010; 86(3): 365-73.
[16]
Kim HD, Kim DJ, Lee IJ, et al. Human fetal heart development after mid-term: morphometry and ultrastructural study. J Mol Cell Cardiol 1992; 24(9): 949-65.
[17]
Kou CY, Lau SL, Au KW, et al. Epigenetic regulation of neonatal cardiomyocytes differentiation. Biochem Biophys Res Commun 2010; 400(2): 278-83.
[18]
Paradis AN, Gay MS, Zhang L, et al. Binucleation of cardiomyocytes: the transition from a proliferative to a terminally differentiated state. Drug Discov Today 2014; 19(5): 602-9.
[19]
Wessels A, Sedmera D. Developmental anatomy of the heart: a tale of mice and man. Physiol Genomics 2003; 15(3): 165-76.
[20]
Rumyantsev PP. Interrelations of the proliferation and differentiation processes during cardiac myogenesis and regeneration. Int Rev Cytol 1977; 51: 186-273.
[21]
Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114(6): 763-76.
[22]
Poss KD, Wilson LG, Keating MT, et al. Heart regeneration in zebrafish. Science 2002; 298(5601): 2188-90.
[23]
Porrello ER, Mahmoud A, Simpson E, et al. Transient regenerative potential of the neonatal mouse heart. Science 2011; 331(6020): 1078-80.
[24]
Yuan X, Braun T. An unexpected switch: regulation of cardiomyocyte proliferation by the homeobox gene meis1. Circ Res 2013; 113(3): 245-8.
[25]
Brooks G, Poolman RA, Li JM, et al. Arresting developments in the cardiac myocyte cell cycle: role of cyclin-dependent kinase inhibitors. Cardiovasc Res 1998; 39(2): 301-11.
[26]
Berthet C, Kaldis P. Cdk2 and Cdk4 cooperatively control the expression of Cdc2. Cell Div 2006; 1: 10.
[27]
Woo RA, Poon RY. Cyclin-Dependent kinases and S phase control in mammalian cells. Cell Cycle 2003; 2(4): 316-24.
[28]
Ciemerych MA, Kenney AM, Sicinska E, et al. Development of mice expressing a single D-type cyclin. Genes Dev 2002; 16(24): 3277-89.
[29]
Diehl JA, Sherr CJ. A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK-activating kinase. Mol Cell Biol 1997; 17(12): 7362-74.
[30]
Sun Q, Zhang F, Wafa K, et al. A splice variant of cyclin D2 regulates cardiomyocyte cell cycle through a novel protein aggregation pathway. J Cell Sci 2009; 122(Pt10): 1563-73.
[31]
Wafa K, MacLean J, Zhang F, et al. Characterization of growth suppressive functions of a splice variant of cyclin D2. PLoS One 2013; 8(1): e53503.
[32]
Blagosklonny MV. Cell senescence: hypertrophic arrest beyond the restriction point. J Cell Physiol 2006; 209(3): 592-7.
[33]
Crescenzi M, Soddu S, Tato F, et al. Mitotic cycle reactivation in terminally differentiated cells by adenovirus infection. J Cell Physiol 1995; 162(1): 26-35.
[34]
Leone M, Magadum A, Engel FB, et al. Cardiomyocyte proliferation in cardiac development and regeneration: a guide to methodologies and interpretations. Am J Physiol Heart Circ Physiol 2015; 309(8): H1237-50.
[35]
Blagosklonny MV. Cell cycle arrest is not senescence. Aging (Albany NY) 2011; 3(2): 94-101.
[36]
Li F, Wang X, Gerdes AM, et al. Formation of binucleated cardiac myocytes in rat heart: II. cytoskeletal organisation. J Mol Cell Cardiol 1997; 29(6): 1553-65.
[37]
Clubb FJ, Bishop SP. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy. Lab Invest 1984; 50(5): 571-7.
[38]
Campisi J. Cell biology: The beginning of the end. Nature 2013; 505: 35-6.
[39]
Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol 2013; 75: 685-705.
[40]
Sdek P, Zhao P, Wang Y, et al. Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes. J Cell Biol 2011; 194(3): 407-23.
[41]
Mahmoud AI, Kocabas F, Muralidhar SA, et al. Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature 2013; 497(7448): 249-53.
[42]
Porrello ER, Mahmoud A, Simpson E, et al. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc Natl Acad Sci USA 2013; 110(1): 187-92.
[43]
Zhang Y, Zhong JF, Qiu H, et al. Epigenomic reprogramming of adult cardiomyocyte-derived cardiac progenitor cells. Sci Rep 2015; 5: 17686.
[44]
Paige SL, Plonowska K, Xu A, et al. Molecular regulation of cardiomyocyte differentiation. Circ Res 2015; 116(2): 341-53.
[45]
Shikama N, Lutz W, Kretzschmar R, et al. Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. EMBO J 2003; 22(19): 5175-85.
[46]
Voss AK, Vanyai HK, Collin C, et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell 2012; 23(3): 652-63.
[47]
McElhinney DB, Driscoll DA, Levin ER, et al. Chromosome 22q11 deletion in patients with ventricular septal defect: frequency and associated cardiovascular anomalies. Pediatrics 2003; 112(6 Pt 1): e472.
[48]
Tane S, Ikenishi A, Okayama H, et al. CDK inhibitors, p21Cip1 and p27Kip1, participate in cell cycle exit of mammalian cardiomyocytes. Biochem Biophys Res Commun 2014; 443(3): 1105-9.
[49]
Ahuja P, Sdek P, Maclellan WR, et al. Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol Rev 2007; 87(2): 521-44.
[50]
Wade Harper J, Adami GR, Wei N, et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993; 75(4): 805-16.
[51]
Xiong Y, Hannon GJ, Zhang H, et al. P21 is a universal inhibitor of cyclin kinases. Nature 1993; 366(6456): 701-4.
[52]
Polyak K, Lee MH, Erdjument-Bromage H, et al. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 1994; 78(1): 59-66.
[53]
Xiong Y, Zhang H, Beach D, et al. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev 1993; 7(8): 1572-83.
[54]
Luo Y, Hurwitz J, Massagué J. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Nature 1995; 375(6527): 159-61.
[55]
Chen J, Jackson PK, Kirschner MW, et al. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 1995; 374(6520): 386-8.
[56]
Li R, Waga S, Hannon GJ, et al. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature 1994; 371: 534-7.
[57]
Noda A, Ning Y, Venable SF, et al. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 1994; 211(1): 90-8.
[58]
Poolman RA, Gilchrist R, Brooks G. Cell cycle profiles and expressions of p21CIP1 AND P27KIP1 during myocyte development. Int J Cardiol 1998; 67(2): 133-42.
[59]
Toyoshima H, Hunter T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 1994; 78(1): 67-74.
[60]
Hengst L, Dulic V, Slingerland JM, et al. A cell cycle-regulated inhibitor of cyclin-dependent kinases. Proc Natl Acad Sci USA 1994; 91(12): 5291-5.
[61]
Lee MH, Reynisdottir I, Massague J, et al. Cloning of p57(KIP2), a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev 1995; 9(6): 639-49.
[62]
Senyo SE, Steinhauser ML, Pizzimenti CL, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature 2013; 493(7432): 433-6.
[63]
Erokhina EL. Proliferation dynamics of cellular elements in the differentiating mouse myocardium. Tsitologiia 1968; 10(11): 1391-409.
[64]
Toyoda M, Shirato H, Nakajima K, et al. Jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression. Dev Cell 2003; 5(1): 85-97.
[65]
Ikenishi A, Okayama H, Iwamoto N, et al. Cell cycle regulation in mouse heart during embryonic and postnatal stages. Dev Growth Differ 2012; 54(8): 731-8.
[66]
Harper JW, Elledge SJ, Keyomarsi K, et al. Inhibition of cyclin-dependent kinases by p21. Mol Biol Cell 1995; 6(4): 387-400.
[67]
Nakanishi T, Markwald RR, Baldwin HS, et al. Etiology and morphogenesis of congenital heart disease from gene function and cellular interaction to morphology, Chapter 11. Tokyo: Springer 2016.
[68]
Medema RH, Herrera RE, Lam F, et al. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc Natl Acad Sci USA 1995; 92(14): 6289-93.
[69]
Li Y, Jenkins CW, Nichols MA, et al. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. Oncogene 1994; 9: 2261-8.
[70]
Poolman RA, Brooks G. Expression of CIP/KIP family of cyclin-dependent kinase inhibitors during cardiac development. Circulation 1996; 94: A0909.
[71]
Burton PBJ, Yacoub MH, Barton PJR, et al. Cyclin-dependent kinase inhibitor expression in human heart failure. A comparison with fetal development. Eur Heart J 1999; 20: 604-11.
[72]
Flink IL, Oana S, Bahl JJ, et al. Terminal differentiation in cardiomyocytes results from hypophosphorylation of retinoblastoma protein by induction of cyclin-dependent kinase inhibitory activities. Circulation 1996; 94: A2745.
[73]
Halevy O, Novitch BG, Spicer DB, et al. Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 1995; 267(5200): 1018-21.
[74]
Capasso JM, Bruno S, Cheng W, et al. Ventricular loading is coupled with DNA synthesis in adult cardiac myocytes after acute and chronic myocardial infarction in rats. Circ Res 1992; 71(6): 1379-89.
[75]
Rumyantsev PP. Proliferative activity of cardiomyocyte and poly-ploidization of their nuclei during myocardial hypertrophy of non-primates n: growth and hyperplasia of cardiac muscle cells, Carlson BM, editor. pp. 231–238. Soviet Medical Reviews Supplement Cardiology.Vol 3. Harwood Academic Press 1991.
[76]
Kimura W, Xiao F, Canseco DC, et al. Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart. Nature 2015; 523(7559): 226-30.
[77]
Simsek T, Kocabas F, Zheng J, et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 2010; 7(3): 380-90.
[78]
Takubo K, Goda N, Yamada W, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells-SOM. Cell Stem Cell 2010; 7(3): 391-402.
[79]
Takubo K, Nagamatsu G, Kobayashi CI, et al. Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell 2013; 12(1): 49-61.
[80]
Bartrons R, Caro J. Hypoxia, glucose metabolism and the Warburg’s effect. J Bioenerg Biomembr 2007; 39(3): 223-9.
[81]
Iyer NV, Kotch LE, Agani F, et al. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev 1998; 12(2): 149-62.
[82]
Wheaton WW, Chandel NS. Hypoxia. 2. Hypoxia regulates cellular metabolism. Am J Physiol Cell Physiol 2011; 300(3): C385-93.
[83]
Kimura W, Muralidhar S, Canseco DC, et al. Redox signaling in cardiac renewal. antioxid. Antioxid Redox Signal 2014; 21(11): 1660-73.
[84]
Vincent SD, Buckingham ME. How to make a heart: The origin and regulation of cardiac progenitor cells. Curr Top Dev Biol 2010; 90: 1-41.
[85]
Tada M, Smith JC. T-targets: clues to understanding the functions of T-box proteins. Dev Growth Differ 2001; 43: 1-11.
[86]
Plageman TF Jr, Yutzey KE. T-box genes and heart development: Putting the “T” in heart. Dev Dyn 2005; 232: 11-20.
[87]
Greulich F, Rudat C, Kispert A, et al. Mechanisms of T-box gene function in the developing heart. Cardiovasc Res 2011; 91: 212-22.
[88]
Chakraborty S, Sengupta A, Yutzey KE, et al. Tbx20 promotes cardiomyocyte proliferation and persistence of fetal characteristics in adult mouse hearts. J Mol Cell Cardiol 2013; 62: 203-13.
[89]
Xiang FL, Guo M, Yutzey KE, et al. Overexpression of Tbx20 in adult cardiomyocytes promotes proliferation and improves cardiac function after myocardial infarction. Circulation 2016; 133(11): 1081-92.
[90]
Halder G, Johnson RL. Hippo signaling: growth control and beyond. Development 2011; 138: 9-22.
[91]
Leach JP, Heallen T, Zhang M, et al. Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 2017; 550(7675): 260-4.
[92]
Morikawa Y, Heallen T, Leach J, et al. Dystrophin-glycoprotein complex sequesters yap to inhibit cardiomyocyte proliferation. Nature 2017; 547(7662): 227-31.
[93]
Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20: 649-88.
[94]
Cheng L, Ding G, Qin Q, et al. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat Med 2004; 10(11): 1245-50.
[95]
Burkart EM, Sambandam N, Han X, et al. Nuclear receptors PPAR beta/delta and PPAR alpha direct distinct metabolic regulatory programs in the mouse heart. J Clin Invest 2007; 117(12): 3930-9.
[96]
Liu J, Wang P, Luo J, et al. Peroxisome proliferator-activated receptor β/δ activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition. Hypertension 2011; 57(2): 223-30.
[97]
Magadum A, Ding Y, He L, et al. Live cell screening platform identifies PPARδ as a regulator of cardiomyocyte proliferation and cardiac repair. Cell Res 2017; 27(8): 1002-19.
[98]
Jayawardena TM, Egemnazarov B, Finch EA, et al. MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 2012; 110(11): 1465-73.
[99]
Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature 2011; 469(7330): 336-42.
[100]
Sluijter JP, van Mil A, van Vliet P, et al. MicroRNA-1 and-499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol 2010; 30(4): 859-68.
[101]
Li X, Wang J, Jia Z, et al. MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac differentiation via Sox6 and cyclin D1. PLoS One 2013; 8(9): e74504.
[102]
Tian Y, Liu Y, Wang T, et al. A micro RNA-Hippo pathway that promotes cardiomyocyte proliferation and cardiac regeneration in mice. Sci Transl Med 2015; 7(279): 279ra38.
[103]
Liu N, Bezprozvannaya S, Williams AH, et al. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev 2008; 22(23): 3242-54.
[104]
Eulalio A, Mano M, Dal Ferro M, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature 2012; 492(7429): 376-81.
[105]
Pandey R, Yang Y, Jackson L, et al. MicroRNAs regulating meis1 expression and inducing cardiomyocyte proliferation. Cardiovasc Regen Med 2016; 3: e1468.
[106]
Wu YH, Zhao H, Zhou LP, et al. miR-134 modulates the proliferation of human cardiomyocyte progenitor cells by targeting Meis2. Int J Mol Sci 2015; 16(10): 25199-213.
[107]
Rizki G, Boyer LA. Lncing epigenetic control of transcription to cardiovascular development and disease. Circ Res 2015; 117(2): 192-206.
[108]
Ounzain S, Pedrazzini T. The promise of enhancer-associated long noncoding RNAs in cardiac regeneration. Trends Cardiovasc Med 2015; 25(7): 592-602.
[109]
Klattenhoff CA, Scheuermann JC, Surface LE, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 2013; 152(3): 570-83.
[110]
Cai B, Ma W, Ding F, et al. The long noncoding RNA CAREL controls cardiac regeneration. J Am Coll Cardiol 2018; 72(5)
[http://dx.doi.org/10.1016/j.jacc.2018.04.085]
[111]
Lopaschuk GD, Jaswal JS. Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation. J Cardiovasc Pharmacol 2010; 56: 130-40.
[112]
Mills RJ, Titmarsh DM, Koenig X, et al. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci USA 2017; 114(40): E8372-81.
[113]
Jesty SA, Steffey MA, Lee FK, et al. C-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult heart. Proc Natl Acad Sci USA 2012; 109: 13380-5.
[114]
Puente BN, Kimura W, Muralidhar SA, et al. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell 2014; 157: 565-79.
[115]
Nakada Y, Canseco DC, Thet S, et al. Hypoxia induces heart regeneration in adult mice. Nature 2017; 541(7636): 222-7.
[116]
Collesi C, Giacca M. Gene transfer to promote cardiac regeneration. Crit Rev Clin Lab Sci 2016; 53(6): 359-69.
[117]
Ylä-Herttuala S, Baker AH. Cardiovascular gene therapy: Past, present, and future. Mol Ther 2017; 25(5): 1095-106.
[118]
Katarzyna R. Adult stem cell therapy for cardiac repair in patients after acute myocardial infarction leading to ischemic heart failure: An overview of evidence from the recent clinical trials. Curr Cardiol Rev 2017; 13(3): 223-31.
[119]
Vera Janavel G, Crottogini A, Cabeza Meckert P, et al. Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep. Gene Ther 2006; 13: 1133-42.
[120]
Vera Janavel GL, De Lorenzi A, Cortés C, et al. Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2 months of coronary artery occlusion. J Gene Med 2012; 14(4): 279-87.
[121]
Laguens R, Cabeza Meckert P, Vera Janavel G, et al. Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer. Gene Ther 2002; 9: 1676-81.
[122]
Laguens R, Cabeza Meckert P, Vera Janavel G, et al. Cardiomyocyte hyperplasia after plasmid-mediated vascular endothelial growth factor gene transfer in pigs with chronic myocardial ischemia. J Gene Med 2004; 6: 222-7.
[123]
Hedman M, Hartikainen J, Yla-Herttuala S, et al. Progress and prospects: hurdles to cardiovascular gene therapy clinical trials. Gene Ther 2011; 18: 743-9.
[124]
Giacca M, Zacchigna S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther 2012; 19: 622-9.
[125]
Olea FD, Vera Janavel G, Cuniberti L, et al. Repeated, but not single, VEGF gene transfer affords protection against ischemic muscle lesions in rabbits with hindlimb ischemia. Gene Ther 2009; 16(6): 716-23.
[126]
Locatelli P, Olea FD, Hnatiuk A, et al. Mesenchymal stromal cells overexpressing vascular endothelial growth factor in ovine myocardial infarction. Gene Ther 2015; 22(6): 449-57.
[127]
Zacchigna S, Zentilin L, Giacca M. Adeno-associated virus vectors as therapeutic and investigational tools in the cardiovascular system. Circ Res 2014; 114: 1827-46.
[128]
Wang C, Zhang B, Lin Y, Dong Y. Effects of adenovirus-mediated VEGF165 gene therapy on myocardial infarction. Ann Clin Lab Sci 2018; 48(2): 208-15.
[129]
Kaski JC, Consuegra-Sanchez L. Evaluation of ASPIRE trial: A Phase III pivotal registration trial, using intracoronary administration of Generx (Ad5FGF4) to treat patients with recurrent angina pectoris. Expert Opin Biol Ther 2013; 13: 1749-53.
[130]
Yang ZJ, Zhang YR, Chen B, et al. Phase I clinical trial on intracoronary administration of Ad-hHGF treating severe coronary artery disease. Mol Biol Rep 2009; 36: 1323-9.
[131]
Hayward C, Banner NR, Morley-Smith A, Lyon AR, Harding SE. The current and future landscape of SERCA gene therapy for heart failure: a clinical perspective. Hum Gene Ther 2015; 26(5): 293-304.
[132]
Creager MA, Olin JW, Belch JJF, et al. Effect of hypoxia-inducible factor-1 alpha gene therapy on walking performance in patients with intermittent claudication. Circulation 2011; 124: 1765-73.
[133]
Hnatiuk AP, Ong SG, Olea FD, et al. Allogeneic mesenchymal stromal cells overexpressing mutant human hypoxia-inducible factor 1-α (hif1-α) in an ovine model of acute myocardial infarction. J Am Heart Assoc 2016; 5(7): pii: e003714.
[134]
Ding J, Lin ZQ, Jiang JM, et al. Preparation of rAAV9 to overexpress or knockdown genes in mouse hearts. J Vis Exp 2016; 118
[135]
Khatiwala RV, Zhang S, Li X, et al. Inhibition of p16INK4A to rejuvenate aging human cardiac progenitor cells via the upregulation of anti-oxidant and NFκB signal pathways. Stem Cell Rev 2018; 14(4): 612-25.
[136]
Cheng YY, Yan YT, Lundy DJ, et al. Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration. EMBO Mol Med 2017; 9(2): 251-64.
[137]
Ghosh AK, Rai R, Flevaris P, Vaughan DE. Epigenetics in reactive and reparative cardiac fibrogenesis: the promise of epigenetic therapy. J Cell Physiol 2017; 232(8): 1941-56.
[138]
Bhuvanalakshmi G, Arfuso F, Kumar AP, Dharmarajan A, Warrier S. Epigenetic reprogramming converts human Wharton’s jelly mesenchymal stem cells into functional cardiomyocytes by differential regulation of Wnt mediators. Stem Cell Res Ther 2017; 8(1): 185.
[139]
Motta BM, Pramstaller PP, Hicks AA, Rossini A. The Impact of CRISPR/Cas9 technology on cardiac research: From disease modelling to therapeutic approaches. Stem Cells Int 2017; 2017: 8960236.
[140]
Lakshmanan R, Krishnan UM, Sethuraman S, et al. Living cardiac patch: the elixir for cardiac regeneration. Expert Opin Biol Ther 2012; 12(12): 1623-40.
[141]
Giménez CS, Locatelli P, Montini Ballarin F, et al. Aligned ovine diaphragmatic myoblasts overexpressing human connexin-43 seeded on poly (L-lactic acid) scaffolds for potential use in cardiac regeneration. Cytotechnology 2018; 70(2): 651-64.
[142]
Perrino C, Barabási AL, Condorelli G, et al. Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? position paper of the european society of cardiology working group on cellular biology of the heart. Cardiovasc Res 2017; 113(7): 725-36.
[143]
Burridge PW, Keller G, Gold JD, Wu JC. Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 2012; 10: 16-28.
[144]
Ginis I, Luo Y, Miura T, et al. Differences between human and mouse embryonic stem cells. Dev Biol 2004; 269: 360-80.
[145]
Broughton KM, Sussman MA. Myocardial regeneration for humans- modifying biology and manipulating evolution. Circ J 2017; 81(2): 142-8.
[146]
Diez-Cuñado M, Wei K, Bushway PJ, et al. miRNAs that induce human cardiomyocyte proliferation converge on the Hippo pathway. Cell Reports 2018; 23(7): 2168-74.
[147]
Gherghiceanu M, Barad L, Novak A, et al. Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure. J Cell Mol Med 2011; 15: 2539-51.
[148]
Lundy SD, Zhu WZ, Regnier M, Laflamme MA. Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev 2013; 22: 1991-2002.
[149]
González-Rosa JM, Sharpe M, Field D, et al. Myocardial polyploidization creates a barrier to heart regeneration in zebrafish. Dev Cell 2018; 44: 433-46.
[150]
Engel FB, Schebesta M, Duong MT, et al. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev 2005; 19(10): 1175-87.

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