Long noncoding RNAs in cardiovascular disease, diagnosis, and therapy.

Stefan Haemmig, Viorel Simion, Dafeng Yang, Yihuan Deng, Mark W Feinberg
Author Information
  1. Stefan Haemmig: aCardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA bDepartment of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan cDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

PURPOSE OF REVIEW: Long noncoding RNAs (lncRNAs) have emerged as powerful regulators of nearly all biological processes. Their cell-type and tissue-specific expression in health and disease provides new avenues for diagnosis and therapy. This review highlights the role of lncRNAs that are involved in cardiovascular disease (CVD) with a special focus on cell types involved in cardiac injury and remodeling, vascular injury, angiogenesis, inflammation, and lipid metabolism.
RECENT FINDINGS: Almost 98% of the genome does not encode for proteins. LncRNAs are among the most abundant type of RNA in the noncoding genome. Accumulating studies have uncovered novel lncRNA-mediated regulation of CVD-associated genes, signaling pathways, and pathophysiological responses. Targeting lncRNAs in vivo using short antisense oligonucleotides or by gene editing has provided important insights into disease pathogenesis through epigenetic, transcriptional, or translational mechanisms. Although cross-species conservation still remains a major obstacle, there is increasing appreciation that altered expression of lncRNAs associates with stage-specific CVD and in human patient cohorts, providing new opportunities for diagnosis and therapy.
SUMMARY: A better understanding of lncRNAs will not only fundamentally improve our understanding of key signaling pathways in CVD, but also aid in the development of effective new therapies and RNA-based biomarkers.

References

  1. Circulation. 1995 Sep 1;92(5):1084-8 [PMID: 7648650]
  2. DNA Cell Biol. 2017 Jun;36(6):475-481 [PMID: 28418724]
  3. Atherosclerosis. 2012 Feb;220(2):449-55 [PMID: 22178423]
  4. Nat Med. 2016 Oct;22(10):1131-1139 [PMID: 27618650]
  5. Biochem Soc Trans. 2011 Apr;39(2):482-6 [PMID: 21428924]
  6. RNA. 2015 May;21(5):801-12 [PMID: 25802408]
  7. FASEB J. 2016 Mar;30(3):1187-97 [PMID: 26578685]
  8. J Cell Sci. 2009 Nov 1;122(Pt 21):3823-30 [PMID: 19889967]
  9. N Engl J Med. 2008 Mar 27;358(13):1370-80 [PMID: 18367740]
  10. Sci Transl Med. 2017 Jun 21;9(395): [PMID: 28637928]
  11. Sci Signal. 2010 Feb 02;3(107):ra8 [PMID: 20124551]
  12. Cardiovasc Res. 1995 May;29(5):689-96 [PMID: 7606759]
  13. J Cell Mol Med. 2015 Jun;19(6):1418-25 [PMID: 25787249]
  14. J Immunol. 2016 Mar 15;196(6):2799-2808 [PMID: 26880762]
  15. Nature. 2014 Oct 2;514(7520):102-106 [PMID: 25119045]
  16. Mol Cell. 2010 Jun 11;38(5):662-74 [PMID: 20541999]
  17. Arterioscler Thromb Vasc Biol. 2010 Mar;30(3):620-7 [PMID: 20056914]
  18. Circ Res. 2013 Nov 8;113(11):1231-41 [PMID: 24047927]
  19. Cell Metab. 2015 Mar 3;21(3):455-67 [PMID: 25738460]
  20. Toxicology. 2017 Jul 1;386:11-18 [PMID: 28526319]
  21. Circ Res. 2014 Apr 25;114(9):1389-97 [PMID: 24602777]
  22. Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1671-7 [PMID: 19592466]
  23. Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 [PMID: 22064851]
  24. Genome Res. 2014 Apr;24(4):616-28 [PMID: 24429298]
  25. J Mol Cell Cardiol. 2015 Dec;89(Pt A):98-112 [PMID: 26423156]
  26. Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):87-101 [PMID: 25265644]
  27. Nature. 2016 May 11;534(7605):124-8 [PMID: 27251289]
  28. Arteriosclerosis. 1986 Mar-Apr;6(2):131-8 [PMID: 2937395]
  29. N Engl J Med. 2007 Aug 2;357(5):443-53 [PMID: 17634449]
  30. Endocrinology. 2010 Jun;151(6):2443-52 [PMID: 20392836]
  31. Biochem Biophys Res Commun. 2016 Feb 26;471(1):135-41 [PMID: 26845358]
  32. Circulation. 2016 May 24;133(21):2050-65 [PMID: 27052414]
  33. J Mol Cell Cardiol. 2016 Feb;91:151-9 [PMID: 26776318]
  34. Diabetes. 2014 Dec;63(12):4249-61 [PMID: 25008173]
  35. Cell Death Dis. 2014 Oct 30;5:e1506 [PMID: 25356875]
  36. Science. 2013 Aug 16;341(6147):789-92 [PMID: 23907535]
  37. Circulation. 2017 Jul 4;136(1):65-79 [PMID: 28351900]
  38. Oncogene. 2011 Apr 21;30(16):1956-62 [PMID: 21151178]
  39. Nature. 2002 Dec 19-26;420(6917):868-74 [PMID: 12490960]
  40. Circ Res. 2014 Apr 25;114(9):1377-88 [PMID: 24557880]
  41. Neuroscience. 2017 Jun 23;354:1-10 [PMID: 28433650]
  42. Nature. 2011 May 19;473(7347):317-25 [PMID: 21593864]
  43. Circ Res. 2017 Feb 17;120(4):620-623 [PMID: 28209793]
  44. N Engl J Med. 2005 Apr 21;352(16):1685-95 [PMID: 15843671]
  45. PLoS One. 2015 Mar 25;10(3):e0120550 [PMID: 25806802]
  46. Hypertension. 2016 Sep;68(3):736-48 [PMID: 27432865]
  47. Sci Transl Med. 2016 Feb 17;8(326):326ra22 [PMID: 26888430]
  48. Cell Signal. 2013 May;25(5):1086-95 [PMID: 23416462]
  49. J Am Coll Cardiol. 2016 Dec 13;68(23):2589-2591 [PMID: 27931619]
  50. Nat Commun. 2014 Apr 07;5:3596 [PMID: 24710105]
  51. Nat Commun. 2016 Aug 19;7:12429 [PMID: 27539542]
  52. Mol Cell. 2015 Jan 8;57(1):39-54 [PMID: 25498145]

Grants

  1. R01 GM115605/NIGMS NIH HHS
  2. R01 HL115141/NHLBI NIH HHS
  3. R01 HL117994/NHLBI NIH HHS
  4. R01 HL134849/NHLBI NIH HHS

MeSH Term

Animals
Cardiovascular Diseases
Endothelial Cells
Humans
Lipid Metabolism
Macrophages
Monocytes
Myocytes, Cardiac
Myocytes, Smooth Muscle
RNA, Long Noncoding

Chemicals

RNA, Long Noncoding

Word Cloud

Created with Highcharts 10.0.0lncRNAsdiseasenoncodingnewdiagnosistherapyCVDLongRNAsexpressioninvolvedcardiovascularinjurygenomesignalingpathwaysunderstandingPURPOSEOFREVIEW:emergedpowerfulregulatorsnearlybiologicalprocessescell-typetissue-specifichealthprovidesavenuesreviewhighlightsrolespecialfocuscelltypescardiacremodelingvascularangiogenesisinflammationlipidmetabolismRECENTFINDINGS:Almost98%encodeproteinsLncRNAsamongabundanttypeRNAAccumulatingstudiesuncoverednovellncRNA-mediatedregulationCVD-associatedgenespathophysiologicalresponsesTargetingvivousingshortantisenseoligonucleotidesgeneeditingprovidedimportantinsightspathogenesisepigenetictranscriptionaltranslationalmechanismsAlthoughcross-speciesconservationstillremainsmajorobstacleincreasingappreciationalteredassociatesstage-specifichumanpatientcohortsprovidingopportunitiesSUMMARY:betterwillfundamentallyimprovekeyalsoaiddevelopmenteffectivetherapiesRNA-basedbiomarkers

Similar Articles

Cited By