Home LiteratureArticle Details
PMID: 23157557 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Functions of microRNAs in cardiovascular biology and disease.

Annual review of physiology ·Vol. 75 ·2013-00-00 ·Pages 69-93

Hata A

Abstract

In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology.

MeSH Terms
Animals Cardiovascular Diseases/physiopathology Cardiovascular Physiological Phenomena Cardiovascular System/embryology,growth & development Cell Communication/physiology Humans MicroRNAs/physiology Morphogenesis/physiology
Chemicals
MicroRNAs
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Hata Akiko
Cardiovascular Research Institute, University of California, San Francisco, California 94158, USA. [email protected]
References (112)
112 references, click to expand
  1. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury.
    Genes Dev. 2009 Sep 15;23(18):2166-78 PMID: 19720868
  2. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements.
    Mol Cell. 2009 Sep 11;35(5):610-25 PMID: 19748357
  3. MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling.
    Circ Res. 2010 Nov 26;107(11):1336-44 PMID: 20947829
  4. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance.
    Dev Cell. 2009 Nov;17(5):662-73 PMID: 19922871
  5. miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy.
    Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12103-8 PMID: 19574461
  6. EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution.
    Development. 2007 Aug;134(16):2913-23 PMID: 17626061
  7. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts.
    Nature. 2008 Dec 18;456(7224):980-4 PMID: 19043405
  8. down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.
    J Biol Chem. 2011 Aug 12;286(32):28097-110 PMID: 21673106
  9. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster.
    J Clin Invest. 2009 Sep;119(9):2634-47 PMID: 19690389
  10. The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient.
    Cell. 2005 Oct 21;123(2):347-58 PMID: 16239150
  11. MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression.
    Cardiovasc Res. 2011 Jan 1;89(1):98-108 PMID: 20736237
  12. MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes.
    Mol Cell. 2011 Sep 16;43(6):993-1004 PMID: 21925387
  13. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13.
    Cell. 2012 Apr 27;149(3):671-83 PMID: 22541436
  14. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation.
    EMBO J. 2007 Aug 8;26(15):3699-708 PMID: 17627278
  15. Biogenesis of small RNAs in animals.
    Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39 PMID: 19165215
  16. Inhibition of miR-15 protects against cardiac ischemic injury.
    Circ Res. 2012 Jan 6;110(1):71-81 PMID: 22052914
  17. Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs.
    Nucleic Acids Res. 2012 Aug;40(14):6391-400 PMID: 22492512
  18. A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples.
    Circ Res. 2012 Jul 20;111(3):290-300 PMID: 22715469
  19. Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype.
    J Biol Chem. 2009 Feb 6;284(6):3728-38 PMID: 19088079
  20. The role of microRNAs in normal and malignant hematopoiesis.
    Eur J Haematol. 2010 Jan 1;84(1):1-16 PMID: 19744129
  21. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis.
    J Exp Med. 2010 Aug 2;207(8):1589-97 PMID: 20643828
  22. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.
    Cell. 2007 Apr 20;129(2):303-17 PMID: 17397913
  23. Circulating microRNAs in patients with coronary artery disease.
    Circ Res. 2010 Sep 3;107(5):677-84 PMID: 20595655
  24. Modulation of microRNA processing by p53.
    Nature. 2009 Jul 23;460(7254):529-33 PMID: 19626115
  25. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects.
    Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2575-86 PMID: 20884876
  26. Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling.
    Circulation. 2008 Oct 7;118(15):1567-76 PMID: 18809798
  27. Transforming growth factor-beta1 (TGF-beta1) utilizes distinct pathways for the transcriptional activation of microRNA 143/145 in human coronary artery smooth muscle cells.
    J Biol Chem. 2011 Aug 26;286(34):30119-29 PMID: 21712382
  28. A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure.
    Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18255-60 PMID: 17108080
  29. Short communication: asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism.
    Circ Res. 2010 Jul 9;107(1):138-43 PMID: 20489163
  30. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs.
    Nat Cell Biol. 2007 May;9(5):604-11 PMID: 17435748
  31. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
    Nat Cell Biol. 2011 Apr;13(4):423-33 PMID: 21423178
  32. MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4.
    Blood. 2008 Jan 15;111(2):588-95 PMID: 17906079
  33. MicroRNAs add a new dimension to cardiovascular disease.
    Circulation. 2010 Mar 2;121(8):1022-32 PMID: 20194875
  34. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.
    Circ Res. 2007 Jun 8;100(11):1579-88 PMID: 17478730
  35. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.
    Genes Dev. 2008 Dec 1;22(23):3242-54 PMID: 19015276
  36. Molecular regulation of vascular smooth muscle cell differentiation in development and disease.
    Physiol Rev. 2004 Jul;84(3):767-801 PMID: 15269336
  37. Posttranscriptional regulation of microRNA biogenesis in animals.
    Mol Cell. 2010 May 14;38(3):323-32 PMID: 20471939
  38. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia.
    Circ Res. 2009 Feb 27;104(4):476-87 PMID: 19150885
  39. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease?
    Circ Res. 2012 Feb 3;110(3):483-95 PMID: 22302755
  40. Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1+ cells.
    Dev Cell. 2012 Jul 17;23(1):45-57 PMID: 22749417
  41. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans.
    Eur Heart J. 2010 Mar;31(6):659-66 PMID: 20159880
  42. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters.
    Cell. 2008 Mar 7;132(5):875-86 PMID: 18329372
  43. MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion.
    Sci Transl Med. 2012 Feb 22;4(122):122ra22 PMID: 22357537
  44. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism.
    Dev Cell. 2010 Dec 14;19(6):903-12 PMID: 21145505
  45. Identification of novel genes coding for small expressed RNAs.
    Science. 2001 Oct 26;294(5543):853-8 PMID: 11679670
  46. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease.
    Cell Death Differ. 2009 Dec;16(12):1590-8 PMID: 19816508
  47. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  48. MicroRNA-15b modulates cellular ATP levels and degenerates mitochondria via Arl2 in neonatal rat cardiac myocytes.
    J Biol Chem. 2010 Feb 12;285(7):4920-30 PMID: 20007690
  49. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence.
    Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14879-84 PMID: 18812516
  50. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
    Cell. 1993 Dec 3;75(5):855-62 PMID: 8252622
  51. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs.
    Nat Cell Biol. 2012 Feb 12;14(3):249-56 PMID: 22327366
  52. Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure.
    Circ Res. 2009 Sep 11;105(6):585-94 PMID: 19679836
  53. Pervasive roles of microRNAs in cardiovascular biology.
    Nature. 2011 Jan 20;469(7330):336-42 PMID: 21248840
  54. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA.
    Mol Cell. 2008 Oct 24;32(2):276-84 PMID: 18951094
  55. Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.
    Blood. 2010 Jun 10;115(23):4944-50 PMID: 20299512
  56. Dysregulation of angiogenesis-related microRNAs in endothelial progenitor cells from patients with coronary artery disease.
    Biochem Biophys Res Commun. 2011 Feb 4;405(1):42-6 PMID: 21195052
  57. MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function.
    Arterioscler Thromb Vasc Biol. 2010 Jun;30(6):1118-26 PMID: 20378849
  58. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes.
    Am J Hum Genet. 2007 Aug;81(2):405-13 PMID: 17668390
  59. An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133.
    Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20844-9 PMID: 18093911
  60. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis.
    Dev Cell. 2008 Aug;15(2):261-71 PMID: 18694565
  61. Mechanisms of control of microRNA biogenesis.
    J Biochem. 2010 Oct;148(4):381-92 PMID: 20833630
  62. MicroRNAs and cardiac pathology.
    Nat Rev Cardiol. 2009 Jun;6(6):419-29 PMID: 19434076
  63. microRNA-138 modulates cardiac patterning during embryonic development.
    Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17830-5 PMID: 19004786
  64. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR.
    Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9667-72 PMID: 17535905
  65. The developmental genetics of congenital heart disease.
    Nature. 2008 Feb 21;451(7181):943-8 PMID: 18288184
  66. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline.
    Arterioscler Thromb Vasc Biol. 2010 Apr;30(4):716-23 PMID: 20110569
  67. MicroRNA-29 in aortic dilation: implications for aneurysm formation.
    Circ Res. 2011 Oct 28;109(10):1115-9 PMID: 21903938
  68. Regulation of zebrafish heart regeneration by miR-133.
    Dev Biol. 2012 May 15;365(2):319-27 PMID: 22374218
  69. Widespread changes in protein synthesis induced by microRNAs.
    Nature. 2008 Sep 4;455(7209):58-63 PMID: 18668040
  70. Cell-cell contact globally activates microRNA biogenesis.
    Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7016-21 PMID: 19359480
  71. Cardiac plasticity.
    N Engl J Med. 2008 Mar 27;358(13):1370-80 PMID: 18367740
  72. MiR-33 contributes to the regulation of cholesterol homeostasis.
    Science. 2010 Jun 18;328(5985):1570-3 PMID: 20466885
  73. Control of stress-dependent cardiac growth and gene expression by a microRNA.
    Science. 2007 Apr 27;316(5824):575-9 PMID: 17379774
  74. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.
    Cell. 2009 Aug 21;138(4):696-708 PMID: 19703396
  75. MicroRNA regulation of smooth muscle gene expression and phenotype.
    Curr Opin Hematol. 2012 May;19(3):224-31 PMID: 22406821
  76. MicroRNAs: target recognition and regulatory functions.
    Cell. 2009 Jan 23;136(2):215-33 PMID: 19167326
  77. The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter".
    Front Genet. 2012 Jan 09;2:107 PMID: 22303401
  78. Maturation of microRNA is hormonally regulated by a nuclear receptor.
    Mol Cell. 2009 Oct 23;36(2):340-7 PMID: 19854141
  79. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection.
    Science. 2010 Jan 8;327(5962):198-201 PMID: 19965718
  80. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure.
    Circulation. 2011 Oct 4;124(14):1537-47 PMID: 21900086
  81. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126.
    Development. 2008 Dec;135(24):3989-93 PMID: 18987025
  82. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis.
    Nature. 2005 Jul 14;436(7048):214-20 PMID: 15951802
  83. Dicer is required for embryonic angiogenesis during mouse development.
    J Biol Chem. 2005 Mar 11;280(10):9330-5 PMID: 15613470
  84. The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis.
    Development. 2010 Jun;137(11):1887-96 PMID: 20460367
  85. miR-126 regulates angiogenic signaling and vascular integrity.
    Dev Cell. 2008 Aug;15(2):272-84 PMID: 18694566
  86. MicroRNA-26a is a novel regulator of vascular smooth muscle cell function.
    J Cell Physiol. 2011 Apr;226(4):1035-43 PMID: 20857419
  87. MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes.
    Circ Res. 2011 Sep 2;109(6):670-9 PMID: 21778430
  88. MiR423-5p as a circulating biomarker for heart failure.
    Circ Res. 2010 Apr 2;106(6):1035-9 PMID: 20185794
  89. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.
    Nature. 2009 Aug 6;460(7256):705-10 PMID: 19578358
  90. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.
    Science. 2009 Jun 26;324(5935):1710-3 PMID: 19460962
  91. SMAD proteins control DROSHA-mediated microRNA maturation.
    Nature. 2008 Jul 3;454(7200):56-61 PMID: 18548003
  92. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice.
    J Clin Invest. 2009 Sep;119(9):2772-86 PMID: 19726871
  93. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20.
    Circulation. 2009 May 5;119(17):2357-2366 PMID: 19380620
  94. MicroRNA regulation of cardiovascular development.
    Circ Res. 2009 Mar 27;104(6):724-32 PMID: 19325160
  95. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis.
    Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):13027-32 PMID: 18723672
  96. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice.
    J Clin Invest. 2010 Nov;120(11):3912-6 PMID: 20978354
  97. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.
    Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2111-6 PMID: 18256189
  98. MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling.
    Circ Res. 2012 Nov 9;111(11):1421-33 PMID: 22955733
  99. miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation.
    Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):87-91 PMID: 20018673
  100. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.
    Nat Genet. 2006 Feb;38(2):228-33 PMID: 16380711
  101. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis.
    Nature. 2010 Apr 22;464(7292):1196-200 PMID: 20364122
  102. LNA-mediated microRNA silencing in non-human primates.
    Nature. 2008 Apr 17;452(7189):896-9 PMID: 18368051
  103. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction.
    Eur Heart J. 2010 Nov;31(22):2765-73 PMID: 20534597
  104. Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation.
    Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2370-7 PMID: 22011749
  105. miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation.
    EMBO Rep. 2011 Jan;12(1):56-62 PMID: 21109779
  106. Expression of miR-146a/b is associated with the Toll-like receptor 4 signal in coronary artery disease: effect of renin-angiotensin system blockade and statins on miRNA-146a/b and Toll-like receptor 4 levels.
    Clin Sci (Lond). 2010 Jul 23;119(9):395-405 PMID: 20524934
  107. Downregulation of miR-199a derepresses hypoxia-inducible factor-1alpha and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes.
    Circ Res. 2009 Apr 10;104(7):879-86 PMID: 19265035
  108. miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes.
    J Exp Med. 2011 Mar 14;208(3):549-60 PMID: 21383058
  109. miR-122 continues to blaze the trail for microRNA therapeutics.
    Mol Ther. 2010 Feb;18(2):240-2 PMID: 20125164
  110. Zebrafish microRNA-126 determines hematopoietic cell fate through c-Myb.
    Leukemia. 2011 Mar;25(3):506-14 PMID: 21079614
  111. Characterization of extracellular circulating microRNA.
    Nucleic Acids Res. 2011 Sep 1;39(16):7223-33 PMID: 21609964
  112. Analysis of microRNA knockouts in mice.
    Hum Mol Genet. 2010 Oct 15;19(R2):R169-75 PMID: 20805106
Article Info
Journal
Annual review of physiology
Abbr.
Annu Rev Physiol
ISSN
1545-1585
DOI
10.1146/annurev-physiol-030212-183737
Email
[email protected]
Published
2013-00-00
Epub
2012-00-13
Pages
69-93
Language
English
Region
United States
NLM ID
0370600
PMCID
PMC5215839
Subset
IM
Grants
NHLBI NIH HHS · R01 HL093154 · United States
NHLBI NIH HHS · R01 HL108317 · United States
External Links
PubMed source DOI: 10.1146/annurev-physiol-030212-183737 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2