Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators
Zhuzhi Wen
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorShaoxin Zheng
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorChangqing Zhou
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorWoliang Yuan
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Jingfeng Wang
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Tong WANG, M.D. and Jingfeng WANG, M.D., Cardiovascular Medicine, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou 510120, China. Tel.: (8620)8133-2430 Fax: (8620)8133-2430. E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Tong Wang
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Tong WANG, M.D. and Jingfeng WANG, M.D., Cardiovascular Medicine, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou 510120, China. Tel.: (8620)8133-2430 Fax: (8620)8133-2430. E-mail: [email protected]; [email protected]Search for more papers by this authorZhuzhi Wen
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorShaoxin Zheng
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorChangqing Zhou
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorWoliang Yuan
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Jingfeng Wang
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Tong WANG, M.D. and Jingfeng WANG, M.D., Cardiovascular Medicine, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou 510120, China. Tel.: (8620)8133-2430 Fax: (8620)8133-2430. E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Tong Wang
The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
Tong WANG, M.D. and Jingfeng WANG, M.D., Cardiovascular Medicine, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou 510120, China. Tel.: (8620)8133-2430 Fax: (8620)8133-2430. E-mail: [email protected]; [email protected]Search for more papers by this authorAbstract
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Introduction
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MiRNAs and MSC differentiation into cardiovascular cells
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MiRNAs and MSC differentiation into CMCs
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MiRNAs and MSC differentiation into vascular cells
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MiRNAs and MSC-mediated paracrine effects
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MiRNAs and MSC-mediated endogenous cardiac regeneration
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MiRNAs and MSC-mediated cardiac contractility
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MiRNAs and MSC-mediated neovascularization
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MiRNAs and MSC-mediated anti-inflammatory effect
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MiRNAs and MSC-mediated anti-apoptotic effect
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MiRNAs and MSC-mediated anti-remodelling effect
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MiRNAs and MSC-mediated cardiac metabolic effect
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MiRNAs and MSC-mediated other potential effects
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MiRNAs and MSC-related cardiac neurogenesis
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MiRNAs and MSC anti-arrhythmic potential
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Preconditioning MSCs with MiRNAs as therapeutic perspectives
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Future directions and concluding remarks
Transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is safe and may improve cardiac function and structural remodelling in patients following myocardial infarction (MI). Cardiovascular cell differentiation and paracrine effects to promote endogenous cardiac regeneration, neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility, may contribute to MSC-based cardiac repair following MI. However, current evidence indicates that the efficacy of MSC transplantation was unsatisfactory, due to the poor viability and massive death of the engrafted MSCs in the infarcted myocardium. MicroRNAs are short endogenous, conserved, non-coding RNAs and important regulators involved in numerous facets of cardiac pathophysiologic processes. There is an obvious involvement of microRNAs in almost every facet of putative repair mechanisms of MSC-based therapy in MI, such as stem cell differentiation, neovascularization, apoptosis, cardiac remodelling, cardiac contractility and arrhythmias, and others. It is proposed that therapeutic modulation of individual cardiovascular microRNA of MSCs, either mimicking or antagonizing microRNA actions, will hopefully enhance MSC therapeutic efficacy. In addition, MSCs may be manipulated to enhance functional microRNA expression or to inhibit aberrant microRNA levels in a paracrine manner. We hypothesize that microRNAs may be used as novel regulators in MSC-based therapy in MI and MSC transplantation by microRNA regulation may represent promising therapeutic strategy for MI patients in the future.
References
- 1 Mollmann H, Nef H, Elsasser A, et al . Stem cells in myocardial infarction: from bench to bedside. Heart. 2009; 95: 508–14.
- 2 Scalbert E, Bril A. Implication of microRNAs in the cardiovascular system. Curr Opin Pharmacol. 2008; 8: 181–8.
- 3 Fasanaro P, Greco S, Ivan M, et al . microRNA: emerging therapeutic targets in acute ischemic diseases. Pharmacol Ther. 2010; 125: 92–104.
- 4 Ohtani K, Dimmeler S. Control of cardiovascular differentiation by microRNAs. Basic Res Cardiol. 2011; 106: 5–11.
- 5 Meder B, Keller A, Vogel B, et al . MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic Res Cardiol. 2011; 106: 13–23.
- 6 Bostjancic E, Zidar N, Glavac D. MicroRNA microarray expression profiling in human myocardial infarction. Dis Markers. 2009; 27: 255–68.
- 7 Corsten MF, Dennert R, Jochems S, et al . Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010; 3: 499–506.
- 8 Dominici M, Le Blanc K, Mueller I, et al . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315–7.
- 9 Wang T, Tang W, Sun S, et al . Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats. J Mol Cell Cardiol. 2009; 46: 378–84.
- 10 Wang T, Tang W, Sun S, et al . Improved outcomes of cardiopulmonary resuscitation in rats with myocardial infarction treated with allogenic bone marrow mesenchymal stem cells. Crit Care Med. 2009; 37: 833–9.
- 11 Wen Z, Zheng S, Zhou C, et al . Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction. J Cell Mol Med. 2011; 15: 1032–43.
- 12 Lakshmipathy U, Hart RP. Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells. 2008; 26: 356–63.
- 13 Goff LA, Boucher S, Ricupero CL, et al . Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis. Exp Hematol. 2008; 36: 1354–69.
- 14 Wilson KD, Hu S, Venkatasubrahmanyam S, et al . Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet. 2010; 3: 426–35.
- 15 Ivey KN, Srivastava D. MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell. 2010; 7: 36–41.
- 16 Zhao Y, Samal E, Srivastava D. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature. 2005; 436: 214–20.
- 17 Valtieri M, Sorrentino A. The mesenchymal stromal cell contribution to homeostasis. J Cell Physiol. 2008; 217: 296–300.
- 18 Collino F, Deregibus MC, Bruno S, et al . Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs. PLoS One. 2010; 5: e11803.
- 19 Koh W, Sheng CT, Tan B, et al . Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics. 2010; 11 Suppl 1: S6.
- 20 Hackl M, Brunner S, Fortschegger K, et al . miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell. 2010; 9: 291–6.
- 21 Wagner W, Horn P, Castoldi M, et al . Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One. 2008; 3: e2213.
- 22 Danielson LS, Menendez S, Attolini CS, et al . A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy. Am J Pathol. 2010; 177: 908–17.
- 23 Xie C, Huang H, Sun X, et al . MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4. Stem Cells Dev. 2011; 20: 205–10.
- 24 Huang H, Xie C, Sun X, et al . miR-10a contributes to retinoid acid-induced smooth muscle cell differentiation. J Biol Chem. 2010; 285: 9383–9.
- 25 Kane NM, Meloni M, Spencer HL, et al . Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2010; 30: 1389–97.
- 26 Cordes KR, Sheehy NT, White MP, et al . miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009; 460: 705–10.
- 27 Bonauer A, Carmona G, Iwasaki M, et al . MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009; 324: 1710–3.
- 28 Nagaya N, Fujii T, Iwase T, et al . Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol. 2004; 287: H2670–6.
- 29 Dong S, Cheng Y, Yang J, et al . MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. J Biol Chem. 2009; 284: 29514–25.
- 30 Camussi G, Deregibus MC, Tetta C. Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic information. Curr Opin Nephrol Hypertens. 2010; 19: 7–12.
- 31 Wang T, Xu Z, Jiang W, et al . Cell-to-cell contact induces mesenchymal stem cell to differentiate into cardiomyocyte and smooth muscle cell. Int J Cardiol. 2006; 109: 74–81.
- 32 Tang J, Wang J, Yang J, et al . Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats. Eur J Cardiothorac Surg. 2009; 36: 644–50.
- 33 Zhang D, Fan GC, Zhou X, et al . Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol. 2008; 44: 281–92.
- 34 Fan M, Chen W, Liu W, et al . The effect of age on the efficacy of human mesenchymal stem cell transplantation after a myocardial infarction. Rejuvenation Res. 2010; 13: 429–38.
- 35 Yu JM, Wu X, Gimble JM, et al . Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow. Aging Cell. 2011; 10: 66–79.
- 36 Chen TS, Lai RC, Lee MM, et al . Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 2010; 38: 215–24.
- 37 Port JD, Sucharov C. Role of MicroRNAs in cardiovascular disease: therapeutic challenges and potentials. J Cardiovasc Pharmacol. 2010; 56: 444–53.
- 38 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: 859–68.
- 39 Wang J, Greene SB, Bonilla-Claudio M, et al . Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell. 2010; 19: 903–12.
- 40 Kapinas K, Kessler C, Ricks T, et al . miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem. 2010; 285: 25221–31.
- 41 Deb A, Davis BH, Guo J, et al . SFRP2 regulates cardiomyogenic differentiation by inhibiting a positive transcriptional autofeedback loop of Wnt3a. Stem Cells. 2008; 26: 35–44.
- 42 Pillai MM, Yang X, Balakrishnan I, et al . MiR-886-3p down regulates CXCL12 (SDF1) expression in human marrow stromal cells. PLoS One. 2010; 5: e14304.
- 43 Zernecke A, Bidzhekov K, Noels H, et al . Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009; 2: ra81.
- 44 Gnecchi M, He H, Noiseux N, et al . Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006; 20: 661–9.
- 45 Sayed D, He M, Hong C, et al . MicroRNA-21 is a downstream effector of AKT that mediates its antiapoptotic effects via suppression of Fas ligand. J Biol Chem. 2010; 285: 20281–90.
- 46 Wang X, Zhang X, Ren XP, et al . MicroRNA-494 targeting both proapoptotic and antiapoptotic proteins protects against ischemia/reperfusion-induced cardiac injury. Circulation. 2010; 122: 1308–18.
- 47 Patrick DM, Montgomery RL, Qi X, et al . Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest. 2010; 120: 3912–6.
- 48 van Rooij E, Sutherland LB, Qi X, et al . Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007; 316: 575–9.
- 49 Nishi H, Ono K, Horie T, et al . MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes. Mol Cell Biol. 2011; 31: 744–55.
- 50 Kuehbacher A, Urbich C, Dimmeler S. Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci. 2008; 29: 12–5.
- 51 Hua Z, Lv Q, Ye W, et al . MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One. 2006; 1: e116.
- 52 Suarez Y, Fernandez-Hernando C, Pober JS, et al . Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007; 100: 1164–73.
- 53 Fish JE, Srivastava D. MicroRNAs: opening a new vein in angiogenesis research. Sci Signal. 2009; 2: pe1.
- 54 Nicoli S, Standley C, Walker P, et al . MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010; 464: 1196–200.
- 55 Wurdinger T, Tannous BA, Saydam O, et al . miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008; 14: 382–93.
- 56 Wang XH, Qian RZ, Zhang W, et al . MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol. 2009; 36: 181–8.
- 57 Weber M, Baker MB, Moore JP, et al . MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun. 2010; 393: 643–8.
- 58 Fleissner F, Jazbutyte V, Fiedler J, et al . Short communication: asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism. Circ Res. 2010; 107: 138–43.
- 59 Wang S, Olson EN. AngiomiRs-key regulators of angiogenesis. Curr Opin Genet Dev. 2009; 19: 205–11.
- 60 Zhou L, Seo KH, Wong HK, et al . MicroRNAs and immune regulatory T cells. Int Immunopharmacol. 2009; 9: 524–7.
- 61 Bishopric NH. Mesenchymal stem cell-derived IL-10 and recovery from infarction: a third pitch for the chord. Circ Res. 2008; 103: 125–7.
- 62 Ma F, Liu X, Li D, et al . MicroRNA-466l upregulates IL-10 expression in TLR-triggered macrophages by antagonizing RNA-binding protein tristetraprolin-mediated IL-10 mRNA degradation. J Immunol. 2010; 184: 6053–9.
- 63 Tome M, Lopez-Romero P, Albo C, et al . miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2011; 18: 985–95.
- 64 Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009; 139: 693–706.
- 65 Guo M, Mao X, Ji Q, et al . miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome. Immunol Cell Biol. 2010; 88: 555–64.
- 66 Fang Y, Shi C, Manduchi E, et al . MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 2010; 107: 13450–5.
- 67 Wang Z, Luo X, Lu Y, et al . miRNAs at the heart of the matter. J Mol Med. 2008; 86: 771–83.
- 68 Tang Y, Zheng J, Sun Y, et al . MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. Int Heart J. 2009; 50: 377–87.
- 69 Li W, Ma N, Ong LL, et al . Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells. 2007; 25: 2118–27.
- 70 Ye Y, Hu Z, Lin Y, et al . Downregulation of microRNA-29 by antisense inhibitors and a PPAR-gamma agonist protects against myocardial ischaemia-reperfusion injury. Cardiovasc Res. 2010; 87: 535–44.
- 71 Cheng Y, Liu X, Zhang S, et al . MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. J Mol Cell Cardiol. 2009; 47: 5–14.
- 72 Kato M, Putta S, Wang M, et al . TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 2009; 11: 881–9.
- 73 Wang X, Zhao T, Huang W, et al . Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells. 2009; 27: 3021–31.
- 74 Chang W, Song BW, Lim S, et al . Mesenchymal stem cells pretreated with delivered Hph-1-Hsp70 protein are protected from hypoxia-mediated cell death and rescue heart functions from myocardial injury. Stem Cells. 2009; 27: 2283–92.
- 75 Ren XP, Wu J, Wang X, et al . MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation. 2009; 119: 2357–66.
- 76 Xu C, Lu Y, Pan Z, et al . The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci. 2007; 120: 3045–52.
- 77 Shan ZX, Lin QX, Fu YH, et al . Upregulated expression of miR-1/miR-206 in a rat model of myocardial infarction. Biochem Biophys Res Commun. 2009; 381: 597–601.
- 78 Mishra PK, Tyagi N, Kundu S, et al . MicroRNAs are involved in homocysteine-induced cardiac remodeling. Cell Biochem Biophys. 2009; 55: 153–62.
- 79 Thum T, Gross C, Fiedler J, et al . MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456: 980–4.
- 80 Wang J, Xu R, Lin F, et al . MicroRNA: novel regulators involved in the remodeling and reverse remodeling of the heart. Cardiology. 2009; 113: 81–8.
- 81 van Rooij E, Sutherland LB, Thatcher JE, et al . Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A. 2008; 105: 13027–32.
- 82 Divakaran V, Adrogue J, Ishiyama M, et al . Adaptive and maladptive effects of SMAD3 signaling in the adult heart after hemodynamic pressure overloading. Circ Heart Fail. 2009; 2: 633–42.
- 83 Duisters RF, Tijsen AJ, Schroen B, et al . miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009; 104: 170–8, 6p following 8.
- 84 Ren G, Li T, Lan JQ, et al . Lentiviral RNAi-induced downregulation of adenosine kinase in human mesenchymal stem cell grafts: a novel perspective for seizure control. Exp Neurol. 2007; 208: 26–37.
- 85 Lu H, Buchan RJ, Cook SA. MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res. 2010; 86: 410–20.
- 86 Yu XY, Song YH, Geng YJ, et al . Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1. Biochem Biophys Res Commun. 2008; 376: 548–52.
- 87 Maisel M, Habisch HJ, Royer L, et al . Genome-wide expression profiling and functional network analysis upon neuroectodermal conversion of human mesenchymal stem cells suggest HIF-1 and miR-124a as important regulators. Exp Cell Res. 2010; 316: 2760–78.
- 88 Liu K, Liu Y, Mo W, et al . MiR-124 regulates early neurogenesis in the optic vesicle and forebrain, targeting NeuroD1. Nucleic Acids Res. 2011; 39: 2867–79.
- 89 Andersson T, Rahman S, Sansom SN, et al . Reversible block of mouse neural stem cell differentiation in the absence of dicer and microRNAs. PLoS One. 2010; 5: e13453.
- 90 Magill ST, Cambronne XA, Luikart BW, et al . microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus. Proc Natl Acad Sci U S A. 2010; 107: 20382–7.
- 91 Beveridge NJ, Tooney PA, Carroll AP, et al . Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal. 2009; 21: 1837–45.
- 92 Liu C, Teng ZQ, Santistevan NJ, et al . Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell. 2010; 6: 433–44.
- 93 Aranha MM, Santos DM, Xavier JM, et al . Apoptosis-associated microRNAs are modulated in mouse, rat and human neural differentiation. BMC Genomics. 2010; 11: 514.
- 94 Yang B, Lu Y, Wang Z. Control of cardiac excitability by microRNAs. Cardiovasc Res. 2008; 79: 571–80.
- 95 Yang B, Lin H, Xiao J, et al . The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med. 2007; 13: 486–91.
- 96 Terentyev D, Belevych AE, Terentyeva R, et al . miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2. Circ Res. 2009; 104: 514–21.
- 97 Luo X, Lin H, Pan Z, et al . Down-regulation of miR-1/miR-133 contributes to re-expression of pacemaker channel genes HCN2 and HCN4 in hypertrophic heart. J Biol Chem. 2008; 283: 20045–52.
- 98 Matkovich SJ, Wang W, Tu Y, et al . MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res. 2010; 106: 166–75.
- 99 Lu Y, Zhang Y, Shan H, et al . MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection. Cardiovasc Res. 2009; 84: 434–41.
- 100 Shan H, Li X, Pan Z, et al . Tanshinone IIA protects against sudden cardiac death induced by lethal arrhythmias via repression of microRNA-1. Br J Pharmacol. 2009; 158: 1227–35.
- 101 Suzuki Y, Kim HW, Ashraf M, et al . Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas. Am J Physiol Heart Circ Physiol. 2010; 299: H1077–82.
- 102 Kim HW, Haider HK, Jiang S, et al . Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem. 2009; 284: 33161–8.
- 103 Nie Y, Han BM, Liu XB, et al . Identification of MicroRNAs involved in hypoxia- and serum deprivation-induced apoptosis in mesenchymal stem cells. Int J Biol Sci. 2011; 7: 762–8.
- 104 van Rooij E, Marshall WS, Olson EN. Toward microRNA-based therapeutics for heart disease: the sense in antisense. Circ Res. 2008; 103: 919–28.
- 105 Liu SP, Fu RH, Yu HH, et al . MicroRNAs regulation modulated self-renewal and lineage differentiation of stem cells. Cell Transplant. 2009; 18: 1039–45.
- 106 Condorelli G, Latronico MV, Dorn GW, 2nd. microRNAs in heart disease: putative novel therapeutic targets? Eur Heart J. 2010; 31: 649–58.