CoChat
Sign Up
Cited by 1,180MicroRNA in disease regulationCongenital heart defects researchCardiac Fibrosis and Remodeling

Pervasive roles of microRNAs in cardiovascular biology

Open access
Small, Eric M., Olson, Eric N.·2011·Nature
DOI 10.1038/nature09783PMC PMC3073349
Open this paper in CoChat — free account

Abstract

First recognized as regulators of development in worms and fruitflies, microRNAs are emerging as pivotal modulators of mammalian cardiovascular development and disease. Individual microRNAs modulate the expression of collections of messenger RNA targets that often have related functions, thereby governing complex biological processes. The wideranging functions of microRNAs in the cardiovascular system have provided new perspectives on disease mechanisms and have revealed intriguing therapeutic targets, as well as diagnostics, for a variety of cardiovascular disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nature09783

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 88

  1. [1]Hill JA Olson EN Cardiac plasticity N. Engl. J. Med 2008 358 1370 1380 18367740
  2. [2]Hoffman JI Kaplan S The incidence of congenital heart disease J. Am. Coll. Cardiol 2002 39 1890 1900 12084585
  3. [3]Bruneau BG The developmental genetics of congenital heart disease Nature 2008 451 943 948 18288184
  4. [4]Cordes KR Srivastava D MicroRNA regulation of cardiovascular development Circ. Res 2009 104 724 732 19325160 PMC2664538
  5. [5]Latronico MV Condorelli G MicroRNAs and cardiac pathology Nature Rev. Cardiol 2009 6 419 429 19434076
  6. [6]Small EM Frost RJ Olson EN MicroRNAs add a new dimension to cardiovascular disease Circulation 2010 121 1022 1032 20194875 PMC2847432
  7. [7]van Rooij E Olson EN MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets J. Clin. Invest 2007 117 2369 2376 17786230 PMC1952642
  8. [8]Liu N Olson EN MicroRNA regulatory networks in cardiovascular development Dev. Cell 2010 18 510 525 20412767 PMC2922691
  9. [9]Ikeda S Altered microRNA expression in human heart disease Physiol. Genomics 2007 31 367 373 17712037
  10. [10]van Rooij E A signature pattern of stress–responsive microRNAs that can evoke cardiac hypertrophy and heart failure Proc. Natl Acad. Sci. USA 2006 103 18255 18260 17108080 PMC1838739 This important paper describes the dynamic regulation of miRNA expression during cardiac stress.
  11. [11]Matkovich SJ Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support Circulation 2009 119 1263 1271 19237659 PMC2749457
  12. [12]Thum T MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure Circulation 2007 116 258 267 17606841
  13. [13]Roy S MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue Cardiovasc. Res 2009 82 21 29 19147652 PMC2652741
  14. [14]van Rooij E Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis Proc. Natl Acad. Sci. USA 2008 105 13027 13032 18723672 PMC2529064
  15. [15]Ji R MicroRNA expression signature and antisense-mediated depletion reveal an essential role of microRNA in vascular neointimal lesion formation Circ. Res 2007 100 1579 1588 17478730
  16. [16]Xin M MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury Genes Dev 2009 23 2166 2178 19720868 PMC2751981
  17. [17]Huang ZP Neppl RL Wang DZ MicroRNAs in cardiac remodeling and disease J. Cardiovasc. Transl. Res 2010 3 212 218 20560042
  18. [18]van Rooij E Marshall WS Olson EN Toward microRNA-based therapeutics for heart disease: the sense in antisense Circ. Res 2008 103 919 928 18948630 PMC2725407
  19. [19]Bartel DP MicroRNAs: target recognition and regulatory functions Cell 2009 136 215 233 19167326 PMC3794896
  20. [20]Filipowicz W Bhattacharyya SN Sonenberg N Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Rev. Genet 2008 9 102 114 18197166
  21. [21]Bartel DP MicroRNAs: genomics, biogenesis, mechanism, and function Cell 2004 116 281 297 14744438
  22. [22]Lutter D Marr C Krumsiek J Lang EW Theis FJ Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects BMC Genomics 2010 11 224 20370903 PMC2865499
  23. [23]Cao G Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways Biochem. Biophys. Res. Commun 2010 396 978 982 20470754
  24. [25]Poliseno L Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation Sci. Signal 2010 3 ra29 20388916 PMC2982149
  25. [26]Barik S An intronic microRNA silences genes that are functionally antagonistic to its host gene Nucleic Acids Res 2008 36 5232 5241 18684991 PMC2532712
  26. [27]Alvarez-Saavedra E Horvitz HR Many families of C. elegans microRNAs are not essential for development or viability Curr. Biol 2010 20 367 373 20096582 PMC2844791
  27. [28]Ambros V MicroRNAs: genetically sensitized worms reveal new secrets Curr. Biol 2010 20 R598 R600 20656201
  28. [29]Brenner JL Jasiewicz KL Fahley AF Kemp BJ Abbott AL Loss of individual microRNAs causes mutant phenotypes in sensitized genetic backgrounds in C. elegans Curr. Biol 2010 20 1321 1325 20579881 PMC2946380 This paper suggests redundant and stress-responsive roles of miRNAs, through using miRNA mutants in Dicer-deficient C. elegans.
  29. [30]Zhao Y Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2 Cell 2007 129 303 317 17397913 This paper demonstrates an important role for an miRNA in heart development by genetic deletion in mice.
  30. [31]Yang B The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 Nature Med 2007 13 486 491 17401374
  31. [32]Luo X 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 20052 18458081
  32. [33]Small EM Regulation of PI3-kinase/Akt signalling by muscle-enriched microRNA-486 Proc. Natl Acad. Sci. USA 2010 107 4218 4223 20142475 PMC2840099
  33. [34]Xu N Papagiannakopoulos T Pan G Thomson JA Kosik KS MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells Cell 2009 137 647 658 19409607
  34. [35]Choi WY Giraldez AJ Schier AF Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430 Science 2007 318 271 274 17761850
  35. [36]Xiao J Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4 J. Cell. Physiol 2007 212 285 292 17516552
  36. [37]Brown BD Naldini L Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications Nature Rev. Genet 2009 10 578 585 19609263
  37. [38]Ebert MS Neilson JR Sharp PA MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells Nature Methods 2007 4 721 726 17694064 PMC3857099
  38. [39]Chen JF Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure Proc. Natl Acad. Sci. USA 2008 105 2111 2116 18256189 PMC2542870
  39. [40]Albinsson S MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function Arterioscler. Thromb. Vasc. Biol 2010 30 1118 1126 20378849 PMC2880481
  40. [41]Rao PK Loss of cardiac microRNA-mediated regulation leads to dilated cardiomyopathy and heart failure Circ. Res 2009 105 585 594 19679836 PMC2828903 Deep sequencing showed that the 18 most abundant cardiac miRNAs account for more than 90% of all miRNAs in the heart.
  41. [42]Brown BD Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state Nature Biotechnol 2007 25 1457 1467 18026085
  42. [43]Liu N An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133 Proc. Natl Acad. Sci. USA 2007 104 20844 20849 18093911 PMC2409229
  43. [44]Zhao Y Samal E Srivastava D Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis Nature 2005 436 214 220 15951802
  44. [45]Ivey KN MicroRNA regulation of cell lineages in mouse and human embryonic stem cells Cell Stem Cell 2008 2 219 229 18371447 PMC2293325
  45. [46]Liu N microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart Genes Dev 2008 22 3242 3254 19015276 PMC2600761
  46. [47]Deacon DC The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis Development 2010 137 1887 1896 20460367
  47. [48]Morton SU microRNA-138 modulates cardiac patterning during embryonic development Proc. Natl Acad. Sci. USA 2008 105 17830 17835 19004786 PMC2582580
  48. [49]Schmidt M EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution Development 2007 134 2913 2923 17626061
  49. [50]Nicoli S MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis Nature 2010 464 1196 1200 20364122 PMC2914488
  50. [51]Kuhnert F Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126 Development 2008 135 3989 3993 18987025
  51. [52]Wang S The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis Dev. Cell 2008 15 261 271 18694565 PMC2685763
  52. [53]Fish JE miR-126 regulates angiogenic signalling and vascular integrity Dev. Cell 2008 15 272 284 18694566 PMC2604134 References 52 and 53 show a crucial role for miR-126 in angiogenesis.
  53. [54]Small EM Sutherland LB Rajagopalan R Wang S Olson EN MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling Circ. Res 2010 107 1336 1344 20947829 PMC2997642
  54. [55]Cordes KR miR-145 and miR-143 regulate smooth muscle cell fate and plasticity Nature 2009 460 705 710 19578358 PMC2769203
  55. [56]Elia L 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 16 1590 1598 19816508 PMC3014107
  56. [57]Boettger T Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster J. Clin. Invest 2009 119 2634 2647 19690389 PMC2735940
  57. [58]Zhao G Yu D Weiss MJ MicroRNAs in erythropoiesis Curr. Opin. Hematol 2010 17 155 162 20216213
  58. [59]Georgantas RW III CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control Proc. Natl Acad. Sci. USA 2007 104 2750 2755 17293455 PMC1796783
  59. [60]O’Carroll D A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway Genes Dev 2007 21 1999 2004 17626790 PMC1948855
  60. [61]Lu J MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors Dev. Cell 2008 14 843 853 18539114 PMC2688789
  61. [62]Wang Q MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4 Blood 2008 111 588 595 17906079
  62. [63]Rasmussen KD The miR-144/451 locus is required for erythroid homeostasis J. Exp. Med 2010 207 1351 1358 20513743 PMC2901075
  63. [64]Johnnidis JB Regulation of progenitor cell proliferation and granulocyte function by microRNA-223 Nature 2008 451 1125 1129 18278031
  64. [65]Patrick DM Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3ζ Genes Dev 2010 24 1614 1619 20679397 PMC2912559
  65. [66]Yu D miR-451 protects against erythroid oxidant stress by repressing 14-3-3ζ Genes Dev 2010 24 1620 1633 20679398 PMC2912560 References 65 and 66 show that miR-451 is required for proper erythroid differentiation, and suggest a potential therapeutic application for targeting miR-451 for degradation.
  66. [67]Callis TE MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice J. Clin. Invest 2009 119 2772 2786 19726871 PMC2735902
  67. [69]van Rooij E Control of stress-dependent cardiac growth and gene expression by a microRNA Science 2007 316 575 579 17379774 The first paper to show a role for an miRNA, miR-208a, in the control of cardiac remodelling, using a genetic knockout.
  68. [70]Care A MicroRNA-133 controls cardiac hypertrophy Nature Med 2007 13 613 618 17468766
  69. [71]van Rooij E A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance Dev. Cell 2009 17 662 673 19922871 PMC2796371
  70. [72]Molkentin JD A calcineurin-dependent transcriptional pathway for cardiac hypertrophy Cell 1998 93 215 228 9568714 PMC4459646
  71. [73]Lin Z miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy Proc. Natl Acad. Sci. USA 2009 106 12103 12108 19574461 PMC2715539
  72. [74]Rane S Downregulation of miR-199a derepresses hypoxia-inducible factor-1α and Sirtuin 1 and recapitulates hypoxia preconditioning in cardiac myocytes Circ. Res 2009 104 879 886 19265035 PMC3332328
  73. [75]Patrick DM Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice J. Clin. Invest 2010 120 3912 3916 20978354 PMC2964990
  74. [76]Fleissner F Asymmetric dimethylarginine impairs angiogenic progenitor cell function in patients with coronary artery disease through a microRNA-21-dependent mechanism Circ. Res 2010 107 138 143 20489163
  75. [77]Bonauer A MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice Science 2009 324 1710 1713 19460962
  76. [78]van Solingen C Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis J. Cell. Mol. Med 2009 13 1577 1585 19120690 PMC3828868
  77. [79]Zernecke A Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection Sci. Signal 2009 2 ra81 19996457
  78. [80]Harris TA Yamakuchi M Ferlito M Mendell JT Lowenstein CJ MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1 Proc. Natl Acad. Sci. USA 2008 105 1516 1521 18227515 PMC2234176
  79. [81]Cheng Y MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation Circ. Res 2009 105 158 166 19542014 PMC2728297
  80. [82]Saunders MA Liang H Li WH Human polymorphism at microRNAs and microRNA target sites Proc. Natl Acad. Sci. USA 2007 104 3300 3305 17360642 PMC1805605
  81. [83]Chen K Rajewsky N Natural selection on human microRNA binding sites inferred from SNP data Nature Genet 2006 38 1452 1456 17072316
  82. [85]Sethupathy P 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 81 405 413 17668390 PMC1950808
  83. [86]Schipper ME van Kuik J de Jonge N Dullens HF de Weger RA Changes in regulatory microRNA expression in myocardium of heart failure patients on left ventricular assist device support J. Heart Lung Transplant 2008 27 1282 1285 19059107
  84. [87]Voellenkle C MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients Physiol. Genomics 2010 42 420 426 20484156
  85. [88]Fichtlscherer S Circulating microRNAs in patients with coronary artery disease Circ. Res 2010 107 677 684 20595655
  86. [89]Ji X Plasma miR-208 as a biomarker of myocardial injury Clin. Chem 2009 55 1944 1949 19696117
  87. [90]Elmen J LNA-mediated microRNA silencing in non-human primates Nature 2008 452 896 899 18368051
  88. [91]Lanford RE Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection Science 2010 327 198 201 19965718 PMC3436126 The first report of therapeutically targeting an miRNA for the treatment of a disease in non-human primates.

Cited by

Sorted by citations

Authors
Small, E. M., & Olson, E. N.
Affiliations
The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-01-19
Volume
469
Issue
7330
Pages
336-342
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09783
PMC
PMC3073349
OpenAlex
W1963906441
Cited by
1,180
References
3
Citations by year
2026: 25 · 2025: 36 · 2024: 37 · 2023: 42 · 2022: 45 · 2021: 57 · 2020: 72 · 2019: 74 · 2018: 92 · 2017: 105 · 2016: 108 · 2015: 112 · 2014: 103 · 2013: 111 · 2012: 104
FWCI
8.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL077439, R01HL093039, R37HL053351)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
microRNA, cardiovascular development, cardiovascular disease, miRNA target genes, therapeutic target, cardiovascular diagnostics, gene expression regulation
MeSH terms
Animals, Blood Vessels, Cardiovascular Diseases, Cardiovascular System, Humans, Mutation, MicroRNAs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review