Functional Long Non-coding RNAs in Vascular Smooth Muscle Cells

  • Amy Leung
  • Kenneth Stapleton
  • Rama NatarajanEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 394)


Increasing evidence shows that long non-coding RNAs (lncRNAs) are not “transcriptional noise” but function in a myriad of biological processes. As such, this rapidly growing class of RNAs is important in both development and disease. Vascular smooth muscle cells are integral cells of the blood vessel wall. They are responsible for relaxation and contraction of the blood vessel and respond to hemodynamic as well as environmental signals to regulate blood pressure. Pathophysiological changes to these cells such as hyperproliferation, hypertrophy, migration, and inflammation contribute to cardiovascular diseases (CVDs) such as restenosis, hypertension, and atherosclerosis. Understanding the molecular mechanisms involved in these pathophysiological changes to VSMCs is paramount to developing therapeutic treatments for various cardiovascular disorders. Recent studies have shown that lncRNAs are key players in the regulation of VSMC functions and phenotype and, perhaps also, in the development of VSMC-related diseases. This chapter describes our current understanding of the functions of lncRNAs in VSMCs. It highlights the emerging role of lncRNAs in VSMC proliferation and apoptosis, their role in contractile and migratory phenotype of VSMCs, and their potential role in VSMC disease states.


Thoracic Aortic Aneurysm Thoracic Aortic Aneurysm VSMC Proliferation Renal Proximal Tubular Epithelial Cell Human VSMCs 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Vascular smooth muscle cells

Ang II

Angiotensin II


Long non-coding RNA




Cardiovascular diseases


Human coronary artery smooth muscle cells.



We gratefully acknowledge funding from the National Institutes of Health, NHLBI and NIDDK (R01 HL106089 (RN), R01 DK 065073 (RN), T32DK007571 (to AL), and K01 DK104993 (AL)). The authors thank Dustin Schones for critically reading this manuscript.


  1. Arasu P, Wightman B, Ruvkun G (1991) Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. Genes Develop 5(10):1825–1833CrossRefPubMedGoogle Scholar
  2. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233. doi: 10.1016/j.cell.2009.01.002 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bell RD, Long X, Lin M, Bergmann JH, Nanda V, Cowan SL, Zhou Q, Han Y, Spector DL, Zheng D, Miano JM (2014) Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA. Arterioscler Thromb Vasc Biol 34(6):1249–1259. doi: 10.1161/ATVBAHA.114.303240 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Berk BC, Corson MA (1997) Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases. Circ Res 80(5):607–616CrossRefPubMedGoogle Scholar
  5. Brasier AR, Recinos A 3rd, Eledrisi MS (2002) Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol 22(8):1257–1266CrossRefPubMedGoogle Scholar
  6. Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M, Tonlorenzi R, Willard HF (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44CrossRefPubMedGoogle Scholar
  7. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Develop 25(18):1915–1927. doi: 10.1101/gad.17446611 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147(2):358–369. doi: 10.1016/j.cell.2011.09.028 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chai S, Chai Q, Danielsen CC, Hjorth P, Nyengaard JR, Ledet T, Yamaguchi Y, Rasmussen LM, Wogensen L (2005) Overexpression of hyaluronan in the tunica media promotes the development of atherosclerosis (Circulation research). Circ Res 96(5):583–591. doi: 10.1161/01.RES.0000158963.37132.8b CrossRefPubMedGoogle Scholar
  10. Chao H, Spicer AP (2005) Natural antisense mRNAs to hyaluronan synthase 2 inhibit hyaluronan biosynthesis and cell proliferation. J Biol Chem 280(30):27513–27522. doi: 10.1074/jbc.M411544200 CrossRefPubMedGoogle Scholar
  11. Congrains A, Kamide K, Katsuya T, Yasuda O, Oguro R, Yamamoto K, Ohishi M, Rakugi H (2012) CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC. Biochem Biophys Res Commun 419(4):612–616. doi: 10.1016/j.bbrc.2012.02.050 CrossRefPubMedGoogle Scholar
  12. Consortium EP, Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermuller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J, Drenkow J, Bell I, Zhao X, Srinivasan KG, Sung WK, Ooi HS, Chiu KP, Foissac S, Alioto T, Brent M, Pachter L, Tress ML, Valencia A, Choo SW, Choo CY, Ucla C, Manzano C, Wyss C, Cheung E, Clark TG, Brown JB, Ganesh M, Patel S, Tammana H, Chrast J, Henrichsen CN, Kai C, Kawai J, Nagalakshmi U, Wu J, Lian Z, Lian J, Newburger P, Zhang X, Bickel P, Mattick JS, Carninci P, Hayashizaki Y, Weissman S, Hubbard T, Myers RM, Rogers J, Stadler PF, Lowe TM, Wei CL, Ruan Y, Struhl K, Gerstein M, Antonarakis SE, Fu Y, Green ED, Karaoz U, Siepel A, Taylor J, Liefer LA, Wetterstrand KA, Good PJ, Feingold EA, Guyer MS, Cooper GM, Asimenos G, Dewey CN, Hou M, Nikolaev S, Montoya-Burgos JI, Loytynoja A, Whelan S, Pardi F, Massingham T, Huang H, Zhang NR, Holmes I, Mullikin JC, Ureta-Vidal A, Paten B, Seringhaus M, Church D, Rosenbloom K, Kent WJ, Stone EA, Program NCS, Baylor College of Medicine Human Genome Sequencing C, Washington University Genome Sequencing C, Broad I, Children’s Hospital Oakland Research I, Batzoglou S, Goldman N, Hardison RC, Haussler D, Miller W, Sidow A, Trinklein ND, Zhang ZD, Barrera L, Stuart R, King DC, Ameur A, Enroth S, Bieda MC, Kim J, Bhinge AA, Jiang N, Liu J, Yao F, Vega VB, Lee CW, Ng P, Shahab A, Yang A, Moqtaderi Z, Zhu Z, Xu X, Squazzo S, Oberley MJ, Inman D, Singer MA, Richmond TA, Munn KJ, Rada-Iglesias A, Wallerman O, Komorowski J, Fowler JC, Couttet P, Bruce AW, Dovey OM, Ellis PD, Langford CF, Nix DA, Euskirchen G, Hartman S, Urban AE, Kraus P, Van Calcar S, Heintzman N, Kim TH, Wang K, Qu C, Hon G, Luna R, Glass CK, Rosenfeld MG, Aldred SF, Cooper SJ, Halees A, Lin JM, Shulha HP, Zhang X, Xu M, Haidar JN, Yu Y, Ruan Y, Iyer VR, Green RD, Wadelius C, Farnham PJ, Ren B, Harte RA, Hinrichs AS, Trumbower H, Clawson H, Hillman-Jackson J, Zweig AS, Smith K, Thakkapallayil A, Barber G, Kuhn RM, Karolchik D, Armengol L, Bird CP, de Bakker PI, Kern AD, Lopez-Bigas N, Martin JD, Stranger BE, Woodroffe A, Davydov E, Dimas A, Eyras E, Hallgrimsdottir IB, Huppert J, Zody MC, Abecasis GR, Estivill X, Bouffard GG, Guan X, Hansen NF, Idol JR, Maduro VV, Maskeri B, McDowell JC, Park M, Thomas PJ, Young AC, Blakesley RW, Muzny DM, Sodergren E, Wheeler DA, Worley KC, Jiang H, Weinstock GM, Gibbs RA, Graves T, Fulton R, Mardis ER, Wilson RK, Clamp M, Cuff J, Gnerre S, Jaffe DB, Chang JL, Lindblad-Toh K, Lander ES, Koriabine M, Nefedov M, Osoegawa K, Yoshinaga Y, Zhu B, de Jong PJ (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447(7146):799–816. doi: 10.1038/nature05874
  13. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460(7256):705–710. doi: 10.1038/nature08195 PubMedPubMedCentralGoogle Scholar
  14. Froberg JE, Yang L, Lee JT (2013) Guided by RNAs: X-inactivation as a model for lncRNA function. J Mol Biol 425(19):3698–3706. doi: 10.1016/j.jmb.2013.06.031 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Grote P, Wittler L, Hendrix D, Koch F, Wahrisch S, Beisaw A, Macura K, Blass G, Kellis M, Werber M, Herrmann BG (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Develop Cell 24(2):206–214. doi: 10.1016/j.devcel.2012.12.012 CrossRefGoogle Scholar
  16. Guttman M, Garber M, Levin JZ, Donaghey J, Robinson J, Adiconis X, Fan L, Koziol MJ, Gnirke A, Nusbaum C, Rinn JL, Lander ES, Regev A (2010) Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat Biotechnol 28(5):503–510. doi: 10.1038/nbt.1633 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Han DK, Khaing ZZ, Pollock RA, Haudenschild CC, Liau G (1996) H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells. J Clin Invest 97(5):1276–1285. doi: 10.1172/jci118543 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Han P, Li W, Lin CH, Yang J, Shang C, Nurnberg ST, Jin KK, Xu W, Lin CY, Lin CJ, Xiong Y, Chien HC, Zhou B, Ashley E, Bernstein D, Chen PS, Chen HS, Quertermous T, Chang CP (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514(7520):102–106. doi: 10.1038/nature13596 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142(3):409–419. doi: 10.1016/j.cell.2010.06.040 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, Saito S, Nakamura Y, Tanaka T (2006) Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 51(12):1087–1099. doi: 10.1007/s10038-006-0070-9 CrossRefPubMedGoogle Scholar
  21. Jin W, Reddy MA, Chen Z, Putta S, Lanting L, Kato M, Park JT, Chandra M, Wang C, Tangirala RK, Natarajan R (2012) Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells. J Biol Chem 287(19):15672–15683. doi: 10.1074/jbc.M111.322669 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermuller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316(5830):1484–1488. doi: 10.1126/science.1138341 CrossRefPubMedGoogle Scholar
  23. Kataoka M, Wang DZ (2014) Non-coding RNAs including miRNAs and lncRNAs in cardiovascular biology and disease. Cells 3(3):883–898. doi: 10.3390/cells3030883 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Kato M, Natarajan R (2014) Diabetic nephropathy–emerging epigenetic mechanisms. Nat Rev Nephrol 10(9):517–530. doi: 10.1038/nrneph.2014.116 CrossRefPubMedGoogle Scholar
  25. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Nat Acad Sci USA 106(28):11667–11672. doi: 10.1073/pnas.0904715106 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Klattenhoff CA, Scheuermann JC, Surface LE, Bradley RK, Fields PA, Steinhauser ML, Ding H, Butty VL, Torrey L, Haas S, Abo R, Tabebordbar M, Lee RT, Burge CB, Boyer LA (2013) Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell 152(3):570–583. doi: 10.1016/j.cell.2013.01.003 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A, Qu K, Lee CS, Flockhart RJ, Groff AF, Chow J, Johnston D, Kim GE, Spitale RC, Flynn RA, Zheng GX, Aiyer S, Raj A, Rinn JL, Chang HY, Khavari PA (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493(7431):231–235. doi: 10.1038/nature11661 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel JB (2012) The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res 95(2):194–204. doi: 10.1093/cvr/cvs135 CrossRefPubMedGoogle Scholar
  29. Lam MT, Cho H, Lesch HP, Gosselin D, Heinz S, Tanaka-Oishi Y, Benner C, Kaikkonen MU, Kim AS, Kosaka M, Lee CY, Watt A, Grossman TR, Rosenfeld MG, Evans RM, Glass CK (2013) Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature 498(7455):511–515. doi: 10.1038/nature12209 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854CrossRefPubMedGoogle Scholar
  31. Leung A, Natarajan R (2014) Noncoding RNAs in vascular disease. Curr Opin Cardiol 29(3):199–206. doi: 10.1097/HCO.0000000000000054 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Leung A, Trac C, Jin W, Lanting L, Akbany A, Saetrom P, Schones DE, Natarajan R (2013) Novel long noncoding RNAs are regulated by angiotensin II in vascular smooth muscle cells. Circ Res 113(3):266–278. doi: 10.1161/CIRCRESAHA.112.300849 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Li W, Notani D, Ma Q, Tanasa B, Nunez E, Chen AY, Merkurjev D, Zhang J, Ohgi K, Song X, Oh S, Kim HS, Glass CK, Rosenfeld MG (2013) Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 498(7455):516–520. doi: 10.1038/nature12210 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C (2009) A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res 104(4):476–487. doi: 10.1161/CIRCRESAHA.108.185363 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Mack CP (2011) Signaling mechanisms that regulate smooth muscle cell differentiation. Arterioscler Thromb Vasc Biol 31(7):1495–1505. doi: 10.1161/ATVBAHA.110.221135 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Maegdefessel L, Rayner KJ, Leeper NJ (2015) MicroRNA regulation of vascular smooth muscle function and phenotype: early career committee contribution. Arterioscler Thromb Vasc Biol 35(1):2–6. doi: 10.1161/ATVBAHA.114.304877 CrossRefPubMedGoogle Scholar
  37. Mehta PK, Griendling KK (2007) Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Amer J Physiol Cell Physiol 292(1):C82–C97. doi: 10.1152/ajpcell.00287.2006 CrossRefGoogle Scholar
  38. Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA, Elkon R, Melo SA, Leveille N, Kalluri R, de Laat W, Agami R (2013) eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol Cell 49(3):524–535. doi: 10.1016/j.molcel.2012.11.021 CrossRefPubMedGoogle Scholar
  39. Michael DR, Phillips AO, Krupa A, Martin J, Redman JE, Altaher A, Neville RD, Webber J, Kim MY, Bowen T (2011) The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell. J Biol Chem 286(22):19523–19532. doi: 10.1074/jbc.M111.233916 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Moran VA, Perera RJ, Khalil AM (2012) Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucl Acids Res 40(14):6391–6400. doi: 10.1093/nar/gks296 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Morris KV, Santoso S, Turner AM, Pastori C, Hawkins PG (2008) Bidirectional transcription directs both transcriptional gene activation and suppression in human cells. PLoS Genet 4(11):e1000258. doi: 10.1371/journal.pgen.1000258 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, Lai F, Zytnicki M, Notredame C, Huang Q, Guigo R, Shiekhattar R (2010) Long noncoding RNAs with enhancer-like function in human cells. Cell 143(1):46–58. doi: 10.1016/j.cell.2010.09.001 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Owens GK (1995) Regulation of differentiation of vascular smooth muscle cells. Physiol Rev 75(3):487–517PubMedGoogle Scholar
  44. Penny GD, Kay GF, Sheardown SA, Rastan S, Brockdorff N (1996) Requirement for Xist in X chromosome inactivation. Nature 379(6561):131–137. doi: 10.1038/379131a0 CrossRefPubMedGoogle Scholar
  45. Reddy MA, Jin W, Villeneuve L, Wang M, Lanting L, Todorov I, Kato M, Natarajan R (2012) Pro-inflammatory role of microrna-200 in vascular smooth muscle cells from diabetic mice. Arterioscler Thromb Vasc Biol 32(3):721–729. doi: 10.1161/ATVBAHA.111.241109 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Riessen R, Wight TN, Pastore C, Henley C, Isner JM (1996) Distribution of hyaluronan during extracellular matrix remodeling in human restenotic arteries and balloon-injured rat carotid arteries. Circulation 93(6):1141–1147CrossRefPubMedGoogle Scholar
  47. Small EM, Olson EN (2011) Pervasive roles of microRNAs in cardiovascular biology. Nature 469(7330):336–342. doi: 10.1038/nature09783 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693. doi: 10.1126/science.1192002 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Vigetti D, Deleonibus S, Moretto P, Bowen T, Fischer JW, Grandoch M, Oberhuber A, Love DC, Hanover JA, Cinquetti R, Karousou E, Viola M, D’Angelo ML, Hascall VC, De Luca G, Passi A (2014) Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation. J Biol Chem 289(42):28816–28826. doi: 10.1074/jbc.M114.597401 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Vigetti D, Deleonibus S, Moretto P, Karousou E, Viola M, Bartolini B, Hascall VC, Tammi M, De Luca G, Passi A (2012) Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis. J Biol Chem 287(42):35544–35555. doi: 10.1074/jbc.M112.402347 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Villeneuve LM, Kato M, Reddy MA, Wang M, Lanting L, Natarajan R (2010) Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1. Diabetes 59(11):2904–2915. doi: 10.2337/db10-0208 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Wang S, Zhang X, Yuan Y, Tan M, Zhang L, Xue X, Yan Y, Han L, Xu Z (2014) BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro. Eur J Cardiothorac Surg Off J Eur Assoc Cardiothorac Surg. doi: 10.1093/ejcts/ezu215 Google Scholar
  53. Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21(6):354–361. doi: 10.1016/j.tcb.2011.04.001 CrossRefPubMedGoogle Scholar
  54. Wightman B, Burglin TR, Gatto J, Arasu P, Ruvkun G (1991) Negative regulatory sequences in the lin-14 3′-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development. Genes Develop 5(10):1813–1824CrossRefPubMedGoogle Scholar
  55. Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, Wentworth BM, Bennett CF, Thornton CA (2012) Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature 488(7409):111–115. doi: 10.1038/nature11362 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, Cai Y, Huang H, Yang Y, Liu Y, Xu Z, He D, Zhang X, Hu X, Pinello L, Zhong D, He F, Yuan GC, Wang DZ, Zeng C (2014) LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 130(17):1452–1465. doi: 10.1161/CIRCULATIONAHA.114.011675 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, Cui H (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451(7175):202–206. doi: 10.1038/nature06468 CrossRefPubMedPubMedCentralGoogle Scholar
  58. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322(5902):750–756. doi: 10.1126/science.1163045 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Diabetes Complications and the Irell and Manella Graduate School of Biological SciencesBeckman Research Institute of City of HopeDuarteUSA

Personalised recommendations