Overview of MicroRNAs in Cardiac Hypertrophy, Fibrosis, and Apoptosis

MicroRNAs (miRNAs) are non-coding RNAs that play essential roles in modulating the gene expression in almost all biological events. In the past decade, the involvement of miRNAs in various cardiovascular disorders has been explored in numerous in vitro and in vivo studies. In this paper, studies focused upon the discovery of miRNAs, their target genes, and functionality are reviewed. The selected miRNAs discussed herein have regulatory effects on target gene expression as demonstrated by miRNA/3′ end untranslated region (3′UTR) interaction assay and/or gain/loss-of-function approaches. The listed miRNA entities are categorized according to the biological relevance of their target genes in relation to three cardiovascular pathologies, namely cardiac hypertrophy, fibrosis, and apoptosis. Furthermore, comparison across 86 studies identified several candidate miRNAs that might be of particular importance in the ontogenesis of cardiovascular diseases as they modulate the expression of clusters of target genes involved in the progression of multiple adverse cardiovascular events. This review illustrates the involvement of miRNAs in diverse biological signaling pathways and provides an overview of current understanding of, and progress of research into, of the roles of miRNAs in cardiovascular health and disease.

[1]  M. Latronico,et al.  microRNAs in cardiovascular diseases: current knowledge and the road ahead. , 2014, Journal of the American College of Cardiology.

[2]  Cheuk-Man Yu,et al.  miR-29b as a therapeutic agent for angiotensin II-induced cardiac fibrosis by targeting TGF-β/Smad3 signaling. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[3]  G. Nuovo,et al.  MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. , 2009, Cardiovascular research.

[4]  Jin Ock Kim,et al.  miR-185 Plays an Anti-Hypertrophic Role in the Heart via Multiple Targets in the Calcium-Signaling Pathways , 2015, PloS one.

[5]  Yanjie Lu,et al.  miR-1 Exacerbates Cardiac Ischemia-Reperfusion Injury in Mouse Models , 2012, PloS one.

[6]  Offer Amir,et al.  Serum levels of microRNAs in patients with heart failure , 2012, European journal of heart failure.

[7]  Hong-Xia Wang,et al.  MicroRNA Let-7i Negatively Regulates Cardiac Inflammation and Fibrosis , 2015, Hypertension.

[8]  Annamaria Colao,et al.  The circulating level of FABP3 is an indirect biomarker of microRNA-1. , 2013, Journal of the American College of Cardiology.

[9]  Maureen A. Sartor,et al.  MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20 , 2009, Circulation.

[10]  Bi-Li Zhang,et al.  Inhibiting microRNA-144 abates oxidative stress and reduces apoptosis in hearts of streptozotocin-induced diabetic mice. , 2015, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[11]  Wei Zhang,et al.  MicroRNA-101 Inhibits Rat Cardiac Hypertrophy by Targeting Rab1a , 2015, Journal of cardiovascular pharmacology.

[12]  Yao‐Hua Song,et al.  Glucose induces apoptosis of cardiomyocytes via microRNA-1 and IGF-1. , 2008, Biochemical and biophysical research communications.

[13]  Da-Zhi Wang,et al.  MicroRNA-22 Regulates Cardiac Hypertrophy and Remodeling in Response to Stress , 2013, Circulation research.

[14]  Qiang Sun,et al.  Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice , 2011, Cell Research.

[15]  Douglas E. Vaughan,et al.  MiR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis , 2016, Circulation.

[16]  U. Laufs,et al.  Role of miR-21 in the pathogenesis of atrial fibrosis , 2012, Basic Research in Cardiology.

[17]  Jincheng Li,et al.  Mitofusin 1 Is Negatively Regulated by MicroRNA 140 in Cardiomyocyte Apoptosis , 2014, Molecular and Cellular Biology.

[18]  Y. Pinto,et al.  Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling , 2008, Circulation.

[19]  T. Peng,et al.  MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by down-regulating Sirt1. , 2011, Cardiovascular research.

[20]  Keiichi Fukuda,et al.  MiR‐133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures , 2014, The EMBO journal.

[21]  Michael T. McManus,et al.  Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 , 2007, Cell.

[22]  D. Catalucci,et al.  NF‐κB mediated miR‐26a regulation in cardiac fibrosis , 2013, Journal of cellular physiology.

[23]  Y. Liao,et al.  Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy , 2015, Oncotarget.

[24]  Chaoqian Xu,et al.  MicroRNA-328 as a regulator of cardiac hypertrophy. , 2014, International journal of cardiology.

[25]  Shi-ming Liu,et al.  MiR-30-Regulated Autophagy Mediates Angiotensin II-Induced Myocardial Hypertrophy , 2013, PloS one.

[26]  V. Cameron,et al.  Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients , 2013, European journal of heart failure.

[27]  Onju Ham,et al.  Up-regulation of miR-26a promotes apoptosis of hypoxic rat neonatal cardiomyocytes by repressing GSK-3β protein expression. , 2012, Biochemical and biophysical research communications.

[28]  S. Harding,et al.  Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis , 2015, Cell Death and Disease.

[29]  Yi-Han Chen,et al.  MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter , 2015, International journal of molecular sciences.

[30]  Yanjie Lu,et al.  MicroRNA-101 Inhibited Postinfarct Cardiac Fibrosis and Improved Left Ventricular Compliance via the FBJ Osteosarcoma Oncogene/Transforming Growth Factor-&bgr;1 Pathway , 2012, Circulation.

[31]  Jeffrey L. Anderson,et al.  ACCF / AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults , 2010 .

[32]  D. Guan,et al.  MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways. , 2013, Biochimica et biophysica acta.

[33]  S. Vatner,et al.  Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes , 2009, Circulation research.

[34]  Yue Jiang,et al.  miR‐145 inhibits isoproterenol‐induced cardiomyocyte hypertrophy by targeting the expression and localization of GATA6 , 2013, FEBS letters.

[35]  E. Bronze-da-Rocha MicroRNAs Expression Profiles in Cardiovascular Diseases , 2014, BioMed research international.

[36]  R. Mutharasan,et al.  microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53-dependent pathways and exerts cytoprotective effects. , 2011, American journal of physiology. Heart and circulatory physiology.

[37]  Danish Sayed,et al.  MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy , 2007, Circulation research.

[38]  L. V. Van Laake,et al.  miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes , 2011, The Journal of experimental medicine.

[39]  Yan Sun,et al.  MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. , 2009, International heart journal.

[40]  J. Ge,et al.  MicroRNA-34a promotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2. , 2013, Current pharmaceutical design.

[41]  C. Tabin,et al.  miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation , 2009, Proceedings of the National Academy of Sciences.

[42]  B. Kasinath,et al.  TGFβ-Stimulated MicroRNA-21 Utilizes PTEN to Orchestrate AKT/mTORC1 Signaling for Mesangial Cell Hypertrophy and Matrix Expansion , 2012, PloS one.

[43]  Jin Ock Kim,et al.  The miR-19a/b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1. , 2014, The Biochemical journal.

[44]  Ping Chen,et al.  miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects on Pdcd4 and Pacs2 , 2014, RNA biology.

[45]  W. Rottbauer,et al.  MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts , 2008, Nature.

[46]  Baofeng Yang,et al.  Elevated plasma microRNA-1 predicts heart failure after acute myocardial infarction. , 2013, International journal of cardiology.

[47]  J. Sanderson,et al.  Micro-RNA and mRNA myocardial tissue expression in biopsy specimen from patients with heart failure. , 2015, International journal of cardiology.

[48]  H. Jiang,et al.  Inhibition of microRNA-101 attenuates hypoxia/reoxygenation‑induced apoptosis through induction of autophagy in H9c2 cardiomyocytes. , 2015, Molecular medicine reports.

[49]  Jeffrey E. Thatcher,et al.  Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis , 2008, Proceedings of the National Academy of Sciences.

[50]  L. Zentilin,et al.  MiR-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors , 2013, Circulation.

[51]  Jun Ren,et al.  IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA-1 and microRNA-133a , 2011, Journal of cellular and molecular medicine.

[52]  Peilong Li,et al.  A Pre-microRNA-149 (miR-149) Genetic Variation Affects miR-149 Maturation and Its Ability to Regulate the Puma Protein in Apoptosis*♦ , 2013, The Journal of Biological Chemistry.

[53]  Ke Hu,et al.  Effects of Downregulation of MicroRNA-181a on H2O2-Induced H9c2 Cell Apoptosis via the Mitochondrial Apoptotic Pathway , 2014, Oxidative medicine and cellular longevity.

[54]  J. Smith,et al.  Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction , 2013, BMC Cardiovascular Disorders.

[55]  S. Elmore Apoptosis: A Review of Programmed Cell Death , 2007, Toxicologic pathology.

[56]  X. Chen,et al.  Reciprocal regulation of miR-23a and lysophosphatidic acid receptor signaling in cardiomyocyte hypertrophy. , 2013, Biochimica et biophysica acta.

[57]  T. Sun,et al.  Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy , 2010, Journal of Cell Science.

[58]  Jing Ye,et al.  miR-34a Modulates Angiotensin II-Induced Myocardial Hypertrophy by Direct Inhibition of ATG9A Expression and Autophagic Activity , 2014, PloS one.

[59]  Q. Cui,et al.  MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1 , 2013, PloS one.

[60]  Onju Ham,et al.  MicroRNA-145 suppresses ROS-induced Ca2+ overload of cardiomyocytes by targeting CaMKIIδ. , 2013, Biochemical and biophysical research communications.

[61]  Xiaoke Yin,et al.  Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. , 2014, The Journal of clinical investigation.

[62]  D Andrews,et al.  Essential versus accessory aspects of cell death: recommendations of the NCCD 2015 , 2014, Cell Death and Differentiation.

[63]  M. Abdellatif,et al.  Thioredoxin 1 Negatively Regulates Angiotensin II–Induced Cardiac Hypertrophy Through Upregulation of miR-98/let-7 , 2011, Circulation research.

[64]  C. Chen,et al.  MicroRNA regulation of unfolded protein response transcription factor XBP1 in the progression of cardiac hypertrophy and heart failure in vivo , 2015, Journal of Translational Medicine.

[65]  Yuhang Liu,et al.  miR-150 regulates high glucose-induced cardiomyocyte hypertrophy by targeting the transcriptional co-activator p300. , 2013, Experimental cell research.

[66]  C. Croce,et al.  A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. , 2016, The Journal of Biological Chemistry.

[67]  R. Duisters,et al.  MIRNA-133 AND MIRNA-30 REGULATE CONNECTIVE TISSUE GROWTH FACTOR: IMPLICATIONS FOR A ROLE OF MIRNAS IN MYOCARDIAL MATRIX REMODELING , 2013 .

[68]  H. Zhang,et al.  Role of miR-1 and miR-133a in myocardial ischemic postconditioning , 2011, Journal of Biomedical Science.

[69]  Jian-Fu Chen,et al.  MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. , 2009, The Journal of clinical investigation.

[70]  T. Thum,et al.  MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure , 2015, European journal of heart failure.

[71]  D. Catalucci,et al.  Reciprocal Regulation of MicroRNA-1 and Insulin-Like Growth Factor-1 Signal Transduction Cascade in Cardiac and Skeletal Muscle in Physiological and Pathological Conditions , 2009, Circulation.

[72]  G. Castelnuovo,et al.  Assessment of psychosocial risk factors is missing in the 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults. , 2011, Journal of the American College of Cardiology.

[73]  M. Medvedovic,et al.  MicroRNA-494 Targeting Both Proapoptotic and Antiapoptotic Proteins Protects Against Ischemia/Reperfusion-Induced Cardiac Injury , 2010, Circulation.

[74]  Danish Sayed,et al.  An antagonism between the AKT and beta-adrenergic signaling pathways mediated through their reciprocal effects on miR-199a-5p. , 2010, Cellular signalling.

[75]  W. Gong,et al.  miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8. , 2015, Cardiovascular research.

[76]  Danish Sayed,et al.  GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy. , 2012, Cardiovascular research.

[77]  Jincheng Li,et al.  miR-30 Regulates Mitochondrial Fission through Targeting p53 and the Dynamin-Related Protein-1 Pathway , 2010, PLoS genetics.

[78]  H. Katus,et al.  MicroRNA-20a inhibits stress-induced cardiomyocyte apoptosis involving its novel target Egln3/PHD3. , 2012, Journal of molecular and cellular cardiology.

[79]  I. Komuro,et al.  Circulating p53-Responsive MicroRNAs Are Predictive Indicators of Heart Failure After Acute Myocardial Infarction , 2013, Circulation research.

[80]  Chunxiang Zhang,et al.  MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. , 2009, Journal of molecular and cellular cardiology.

[81]  B. Long,et al.  Cardiac Hypertrophy Is Positively Regulated by MicroRNA miR-23a* , 2011, The Journal of Biological Chemistry.

[82]  Danish Sayed,et al.  MicroRNA-21 Is a Downstream Effector of AKT That Mediates Its Antiapoptotic Effects via Suppression of Fas Ligand* , 2010, The Journal of Biological Chemistry.

[83]  Chaoqian Xu,et al.  β-Blocker carvedilol protects cardiomyocytes against oxidative stress-induced apoptosis by up-regulating miR-133 expression. , 2014, Journal of molecular and cellular cardiology.

[84]  Qing Jing,et al.  Attenuation of MicroRNA‐22 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy , 2012, Journal of cellular physiology.

[85]  E. Olson,et al.  MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca²⁺ overload and cell death. , 2012, The Journal of clinical investigation.

[86]  K. Chowdhury,et al.  The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy , 2012, Nature Communications.

[87]  V. Kim,et al.  Regulation of microRNA biogenesis , 2014, Nature Reviews Molecular Cell Biology.

[88]  Ruotian Li,et al.  MicroRNA-145 Protects Cardiomyocytes against Hydrogen Peroxide (H2O2)-Induced Apoptosis through Targeting the Mitochondria Apoptotic Pathway , 2012, PloS one.

[89]  Soonchang Hong,et al.  Na(+)-Ca(2+) exchanger targeting miR-132 prevents apoptosis of cardiomyocytes under hypoxic condition by suppressing Ca(2+) overload. , 2015, Biochemical and biophysical research communications.

[90]  G. Condorelli,et al.  MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling , 2010, Nature Cell Biology.

[91]  Gianpaolo Zerbini,et al.  MiR‐133a regulates collagen 1A1: Potential role of miR‐133a in myocardial fibrosis in angiotensin II‐dependent hypertension , 2012, Journal of cellular physiology.

[92]  Shengshou Hu,et al.  MicroRNA-24 regulates cardiac fibrosis after myocardial infarction , 2012, Journal of cellular and molecular medicine.

[93]  Chuanyu Wei,et al.  NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2 , 2014, Molecular and Cellular Biochemistry.

[94]  Chaoqian Xu,et al.  MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy , 2014, Cell Death and Disease.

[95]  L. Bu,et al.  MicroRNA-22 Downregulation by Atorvastatin in a Mouse Model of Cardiac Hypertrophy: a new Mechanism for Antihypertrophic Intervention , 2013, Cellular Physiology and Biochemistry.

[96]  C. Croce,et al.  Unique MicroRNA Profile in End-stage Heart Failure Indicates Alterations in Specific Cardiovascular Signaling Networks* , 2009, The Journal of Biological Chemistry.

[97]  H. Weiner Aldehyde dehydrogenase. , 1982, Progress in clinical and biological research.

[98]  He Huang,et al.  MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1 , 2016, Journal of cardiovascular pharmacology and therapeutics.

[99]  Li Lin,et al.  Overexpression of microRNA-378 attenuates ischemia-induced apoptosis by inhibiting caspase-3 expression in cardiac myocytes , 2011, Apoptosis.

[100]  Chaoqian Xu,et al.  By Targeting Stat3 microRNA-17-5p Promotes Cardiomyocyte Apoptosis in Response to Ischemia Followed by Reperfusion , 2014, Cellular Physiology and Biochemistry.

[101]  Feng-lan Li,et al.  Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice. , 2013, Gene.

[102]  J. Nerbonne,et al.  MicroRNA-133a Protects Against Myocardial Fibrosis and Modulates Electrical Repolarization Without Affecting Hypertrophy in Pressure-Overloaded Adult Hearts , 2010, Circulation research.

[103]  P. Liu,et al.  miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway. , 2013, Biochemical and biophysical research communications.

[104]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[105]  B. Long,et al.  miR-9 and NFATc3 Regulate Myocardin in Cardiac Hypertrophy* , 2010, The Journal of Biological Chemistry.

[106]  E. Paul,et al.  MicroRNA-19b Associates with Ago2 in the Amygdala Following Chronic Stress and Regulates the Adrenergic Receptor Beta 1 , 2014, The Journal of Neuroscience.

[107]  Thomas Thum,et al.  Review focus on the role of microRNA in cardiovascular biology and disease. , 2012, Cardiovascular research.

[108]  Jin Ock Kim,et al.  miR-185 inhibits endoplasmic reticulum stress-induced apoptosis by targeting Na+/H+ exchanger-1 in the heart , 2016, BMB reports.

[109]  Gonghui Li,et al.  Downregulation of microRNA-100 protects H2O2-induced apoptosis in neonatal cardiomyocytes. , 2015, International journal of clinical and experimental pathology.

[110]  L. Vardy,et al.  Natriuretic peptide receptor 3 (NPR3) is regulated by microRNA-100. , 2015, Journal of molecular and cellular cardiology.

[111]  R. Hui,et al.  MiR‐221 promotes cardiac hypertrophy in vitro through the modulation of p27 expression , 2012, Journal of cellular biochemistry.

[112]  Kan Yang,et al.  microRNA-21 protects against ischemia-reperfusion and hypoxia-reperfusion-induced cardiocyte apoptosis via the phosphatase and tensin homolog/Akt-dependent mechanism. , 2014, Molecular medicine reports.

[113]  K. Hong,et al.  MicroRNA-223 Displays a Protective Role Against Cardiomyocyte Hypertrophy by Targeting Cardiac Troponin I-Interacting Kinase , 2015, Cellular Physiology and Biochemistry.

[114]  B. Long,et al.  CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation , 2014, Nature Communications.

[115]  H. Bian,et al.  MicroRNA-7a/b Protects against Cardiac Myocyte Injury in Ischemia/Reperfusion by Targeting Poly(ADP-Ribose) Polymerase , 2014, PloS one.

[116]  S. Gupta,et al.  NF-κB mediated miR-21 regulation in cardiomyocytes apoptosis under oxidative stress , 2014, Free radical research.

[117]  I. Karakikes,et al.  Therapeutic Cardiac‐Targeted Delivery of miR‐1 Reverses Pressure Overload–Induced Cardiac Hypertrophy and Attenuates Pathological Remodeling , 2013, Journal of the American Heart Association.

[118]  Qiang Zhao,et al.  MicroRNA-92a Inhibition Attenuates Hypoxia/Reoxygenation-Induced Myocardiocyte Apoptosis by Targeting Smad7 , 2014, PloS one.

[119]  C. Zhai,et al.  A feedback regulatory loop between HIF‐1α and miR‐21 in response to hypoxia in cardiomyocytes , 2014, FEBS letters.

[120]  Seahyoung Lee,et al.  MicroRNA-17-mediated down-regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes. , 2015, Biochemical and biophysical research communications.

[121]  Akshay S. Desai,et al.  Regional Variation in Patients and Outcomes in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) Trial , 2015, Circulation.

[122]  Fen Hu,et al.  MicroRNA-101a Inhibits Cardiac Fibrosis Induced by Hypoxia via Targeting TGFβRI on Cardiac Fibroblasts , 2015, Cellular Physiology and Biochemistry.

[123]  Xiuhua Liu,et al.  MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway , 2013, Apoptosis.

[124]  B. Long,et al.  miR-761 regulates the mitochondrial network by targeting mitochondrial fission factor. , 2013, Free radical biology & medicine.

[125]  Zahi A Fayad,et al.  2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2010, Circulation.

[126]  M. 明,et al.  MicroRNA-34a regulates high glucose-induced apoptosis in H9c2 cardiomyocytes , 2013, Journal of Huazhong University of Science and Technology [Medical Sciences].

[127]  N. Hou,et al.  miR-199a impairs autophagy and induces cardiac hypertrophy through mTOR activation , 2015, Cell Death and Differentiation.