1932

Abstract

The maladaptation of endothelial cells to disturbed flow at arterial bifurcations increases permeability for lipoproteins. Additional injury by chemically modified lipoproteins disrupts the continuous repair of maladapted endothelial cells and triggers intimal macrophage accumulation. Macrophages remove modified lipoproteins from the extracellular space until the cholesterol overload leads to macrophage death and insufficient efferocytosis. This macrophage failure promotes the progression to advanced lesions by formation of a lipid-rich necrotic core, which may rupture and cause myocardial infarction and stroke. In this article, we summarize the fundamental roles of microRNAs (miRNAs) in the regulation of endothelial maladaptation and macrophage failure during atherosclerosis. We describe how miRNAs coordinate the mutual interaction between chronic endothelial repair and endothelial senescence and mechanistically link the regulation of macrophage cholesterol homeostasis with defective efferocytosis. Lastly, we discuss how miRNAs may challenge and extend current theories about atherosclerosis.

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2016-05-23
2024-04-23
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Literature Cited

  1. Ando J, Yamamoto K. 1.  2011. Effects of shear stress and stretch on endothelial function. Antioxid. Redox Signal. 15:1389–403 [Google Scholar]
  2. Garcia-Cardena G, Comander J, Anderson KR, Blackman BR, Gimbrone MA Jr.. 2.  2001. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. PNAS 98:4478–85 [Google Scholar]
  3. Dekker RJ, van Thienen JV, Rohlena J, de Jager SC, Elderkamp YW. 3.  et al. 2005. Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am. J. Pathol. 167:609–18 [Google Scholar]
  4. Dekker RJ, Boon RA, Rondaij MG, Kragt A, Volger OL. 4.  et al. 2006. KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium. Blood 107:4354–63 [Google Scholar]
  5. Zhou G, Hamik A, Nayak L, Tian H, Shi H. 5.  et al. 2012. Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice. J. Clin. Investig. 122:4727–31 [Google Scholar]
  6. Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET. 6.  et al. 2006. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Investig. 116:49–58 [Google Scholar]
  7. Bjorkerud S, Bondjers G. 7.  1972. Endothelial integrity and viability in the aorta of the normal rabbit and rat as evaluated with dye exclusion tests and interference contrast microscopy. Atherosclerosis 15:285–300 [Google Scholar]
  8. Zeng L, Zampetaki A, Margariti A, Pepe AE, Alam S. 8.  et al. 2009. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. PNAS 106:8326–31 [Google Scholar]
  9. Sakao S, Taraseviciene-Stewart L, Lee JD, Wood K, Cool CD, Voelkel NF. 9.  2005. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J. 19:1178–80 [Google Scholar]
  10. Hansson GK, Schwartz SM. 10.  1983. Evidence for cell death in the vascular endothelium in vivo and in vitro. Am. J. Pathol. 112:278–86 [Google Scholar]
  11. Wright HP. 11.  1968. Endothelial mitosis around aortic branches in normal guinea pigs. Nature 220:78–79 [Google Scholar]
  12. Schober A, Nazari-Jahantigh M, Wei Y, Bidzhekov K, Gremse F. 12.  et al. 2014. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat. Med. 20:368–76 [Google Scholar]
  13. Vyalov S, Langille BL, Gotlieb AI. 13.  1996. Decreased blood flow rate disrupts endothelial repair in vivo. Am. J. Pathol. 149:2107–18 [Google Scholar]
  14. Nielsen LB. 14.  1996. Transfer of low density lipoprotein into the arterial wall and risk of atherosclerosis. Atherosclerosis 123:1–15 [Google Scholar]
  15. Chen YL, Jan KM, Lin HS, Chien S. 15.  1997. Relationship between endothelial cell turnover and permeability to horseradish peroxidase. Atherosclerosis 133:7–14 [Google Scholar]
  16. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr. 16.  et al. 1994. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler. Thromb. 14:840–56 [Google Scholar]
  17. Nakashima Y, Fujii H, Sumiyoshi S, Wight TN, Sueishi K. 17.  2007. Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler. Thromb. Vasc. Biol. 27:1159–65 [Google Scholar]
  18. Stary HC. 18.  1987. Macrophages, macrophage foam cells, and eccentric intimal thickening in the coronary arteries of young children. Atherosclerosis 64:91–108 [Google Scholar]
  19. Kolpakov V, Polishchuk R, Bannykh S, Rekhter M, Solovjev P. 19.  et al. 1996. Atherosclerosis-prone branch regions in human aorta: microarchitecture and cell composition of intima. Atherosclerosis 122:173–89 [Google Scholar]
  20. Stary HC. 20.  1990. The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur. Heart J. 11:Suppl. E3–19 [Google Scholar]
  21. Witztum JL, Lichtman AH. 21.  2014. The influence of innate and adaptive immune responses on atherosclerosis. Annu. Rev. Pathol. 9:73–102 [Google Scholar]
  22. Zhou Z, Subramanian P, Sevilmis G, Globke B, Soehnlein O. 22.  et al. 2011. Lipoprotein-derived lysophosphatidic acid promotes atherosclerosis by releasing CXCL1 from the endothelium. Cell Metab. 13:592–600 [Google Scholar]
  23. Hansson GK, Hermansson A. 23.  2011. The immune system in atherosclerosis. Nat. Immunol. 12:204–12 [Google Scholar]
  24. Randolph GJ. 24.  2014. Mechanisms that regulate macrophage burden in atherosclerosis. Circ. Res. 114:1757–71 [Google Scholar]
  25. Robbins CS, Hilgendorf I, Weber GF, Theurl I, Iwamoto Y. 25.  et al. 2013. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19:1166–72 [Google Scholar]
  26. Levitan I, Volkov S, Subbaiah PV. 26.  2010. Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxid. Redox Signal. 13:39–75 [Google Scholar]
  27. Strong JP, Malcom GT, McMahan CA, Tracy RE, Newman WP. 27. , 3rd. et al. 1999. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA 281:727–35 [Google Scholar]
  28. Stary HC. 28.  2000. Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler. Thromb. Vasc. Biol. 20:1177–78 [Google Scholar]
  29. Finlayson R, Symons C, Fiennes RN. 29.  1962. Atherosclerosis: a comparative study. Br. Med. J. 1:501–7 [Google Scholar]
  30. Bohorquez F, Stout C. 30.  1972. Arteriosclerosis in exotic mammals. Atherosclerosis 16:225–31 [Google Scholar]
  31. Schmidt SP, House EW. 31.  1979. Time study of coronary myointimal hyperplasia in precocious male steelhead trout, Salmo gairdneri. Atherosclerosis 34:375–81 [Google Scholar]
  32. Farrell AP, Saunders RL, Freeman HC, Mommsen TP. 32.  1986. Arteriosclerosis in Atlantic salmon. Effects of dietary cholesterol and maturation. Arteriosclerosis 6:453–61 [Google Scholar]
  33. Fernandez-Friera L, Penalvo JL, Fernandez-Ortiz A, Ibanez B, Lopez-Melgar B. 33.  et al. 2015. Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) study. Circulation 131:2104–13 [Google Scholar]
  34. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K. 34.  et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet 380:2095–128 [Google Scholar]
  35. Schmermund A, Schwartz RS, Adamzik M, Sangiorgi G, Pfeifer EA. 35.  et al. 2001. Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with ‘healthy’ subjects dying out of hospital. Atherosclerosis 155:499–508 [Google Scholar]
  36. Bentzon JF, Otsuka F, Virmani R, Falk E. 36.  2014. Mechanisms of plaque formation and rupture. Circ. Res. 114:1852–66 [Google Scholar]
  37. Guyton JR, Klemp KF. 37.  1996. Development of the lipid-rich core in human atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 16:4–11 [Google Scholar]
  38. Felton CV, Crook D, Davies MJ, Oliver MF. 38.  1997. Relation of plaque lipid composition and morphology to the stability of human aortic plaques. Arterioscler. Thromb. Vasc. Biol. 17:1337–45 [Google Scholar]
  39. Hegyi L, Skepper JN, Cary NR, Mitchinson MJ. 39.  1996. Foam cell apoptosis and the development of the lipid core of human atherosclerosis. J. Pathol. 180:423–29 [Google Scholar]
  40. Kolodgie FD, Burke AP, Nakazawa G, Cheng Q, Xu X, Virmani R. 40.  2007. Free cholesterol in atherosclerotic plaques: Where does it come from?. Curr. Opin. Lipidol. 18:500–7 [Google Scholar]
  41. Maor I, Aviram M. 41.  1994. Oxidized low density lipoprotein leads to macrophage accumulation of unesterified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesteryl ester. J. Lipid Res. 35:803–19 [Google Scholar]
  42. Maxfield FR, Tabas I. 42.  2005. Role of cholesterol and lipid organization in disease. Nature 438:612–21 [Google Scholar]
  43. Seimon TA, Obstfeld A, Moore KJ, Golenbock DT, Tabas I. 43.  2006. Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages. PNAS 103:19794–99 [Google Scholar]
  44. Seimon TA, Nadolski MJ, Liao X, Magallon J, Nguyen M. 44.  et al. 2010. Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell Metab. 12:467–82 [Google Scholar]
  45. Ball RY, Stowers EC, Burton JH, Cary NR, Skepper JN, Mitchinson MJ. 45.  1995. Evidence that the death of macrophage foam cells contributes to the lipid core of atheroma. Atherosclerosis 114:45–54 [Google Scholar]
  46. Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet JM, Tedgui A. 46.  1999. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 99:348–53 [Google Scholar]
  47. Reininger AJ, Bernlochner I, Penz SM, Ravanat C, Smethurst P. 47.  et al. 2010. A 2-step mechanism of arterial thrombus formation induced by human atherosclerotic plaques. J. Am. Coll. Cardiol. 55:1147–58 [Google Scholar]
  48. Kellner-Weibel G, Yancey PG, Jerome WG, Walser T, Mason RP. 48.  et al. 1999. Crystallization of free cholesterol in model macrophage foam cells. Arterioscler. Thromb. Vasc. Biol. 19:1891–98 [Google Scholar]
  49. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G. 49.  et al. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357–61 [Google Scholar]
  50. Lima H Jr, Jacobson LS, Goldberg MF, Chandran K, Diaz-Griffero F. 50.  et al. 2013. Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle 12:1868–78 [Google Scholar]
  51. Abela GS, Aziz K, Vedre A, Pathak DR, Talbott JD, Dejong J. 51.  2009. Effect of cholesterol crystals on plaques and intima in arteries of patients with acute coronary and cerebrovascular syndromes. Am. J. Cardiol. 103:959–68 [Google Scholar]
  52. Bremmelgaard A, Stender S, Lorentzen J, Kjeldsen K. 52.  1986. In vivo flux of plasma cholesterol into human abdominal aorta with advanced atherosclerosis. Arteriosclerosis 6:442–52 [Google Scholar]
  53. Tricot O, Mallat Z, Heymes C, Belmin J, Leseche G, Tedgui A. 53.  2000. Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 101:2450–53 [Google Scholar]
  54. Davies MJ, Woolf N, Rowles PM, Pepper J. 54.  1988. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br. Heart J. 60:459–64 [Google Scholar]
  55. Nishi K, Itabe H, Uno M, Kitazato KT, Horiguchi H. 55.  et al. 2002. Oxidized LDL in carotid plaques and plasma associates with plaque instability. Arterioscler. Thromb. Vasc. Biol. 22:1649–54 [Google Scholar]
  56. Volger OL, Fledderus JO, Kisters N, Fontijn RD, Moerland PD. 56.  et al. 2007. Distinctive expression of chemokines and transforming growth factor-β signaling in human arterial endothelium during atherosclerosis. Am. J. Pathol. 171:326–37 [Google Scholar]
  57. Durand E, Scoazec A, Lafont A, Boddaert J, Al Hajzen A. 57.  et al. 2004. In vivo induction of endothelial apoptosis leads to vessel thrombosis and endothelial denudation: a clue to the understanding of the mechanisms of thrombotic plaque erosion. Circulation 109:2503–6 [Google Scholar]
  58. Ross R, Wight TN, Strandness E, Thiele B. 58.  1984. Human atherosclerosis. I. Cell constitution and characteristics of advanced lesions of the superficial femoral artery. Am. J. Pathol. 114:79–93 [Google Scholar]
  59. Kolodgie FD, Narula J, Burke AP, Haider N, Farb A. 59.  et al. 2000. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am. J. Pathol. 157:1259–68 [Google Scholar]
  60. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A. 60.  et al. 1995. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 92:1565–69 [Google Scholar]
  61. Ruvkun G. 61.  2008. The perfect storm of tiny RNAs. Nat. Med. 14:1041–45 [Google Scholar]
  62. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. 62.  2008. Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63 [Google Scholar]
  63. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. 63.  2008. The impact of microRNAs on protein output. Nature 455:64–71 [Google Scholar]
  64. Osella M, Bosia C, Cora D, Caselle M. 64.  2011. The role of incoherent microRNA-mediated feedforward loops in noise buffering. PLOS Comput. Biol. 7:e1001101 [Google Scholar]
  65. Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T. 65.  et al. 2008. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521–33 [Google Scholar]
  66. Li X, Cassidy JJ, Reinke CA, Fischboeck S, Carthew RW. 66.  2009. A microRNA imparts robustness against environmental fluctuation during development. Cell 137:273–82 [Google Scholar]
  67. Hornstein E, Shomron N. 67.  2006. Canalization of development by microRNAs. Nat. Genet. 38:Suppl.S20–24 [Google Scholar]
  68. Berezikov E. 68.  2011. Evolution of microRNA diversity and regulation in animals. Nat. Rev. Genet. 12:846–60 [Google Scholar]
  69. Heimberg AM, Sempere LF, Moy VN, Donoghue PC, Peterson KJ. 69.  2008. MicroRNAs and the advent of vertebrate morphological complexity. PNAS 105:2946–50 [Google Scholar]
  70. Prochnik SE, Rokhsar DS, Aboobaker AA. 70.  2007. Evidence for a microRNA expansion in the bilaterian ancestor. Dev. Genes Evol. 217:73–77 [Google Scholar]
  71. Hertel J, Lindemeyer M, Missal K, Fried C, Tanzer A. 71.  et al. 2006. The expansion of the metazoan microRNA repertoire. BMC Genomics 7:25 [Google Scholar]
  72. Pelaez N, Carthew RW. 72.  2012. Biological robustness and the role of microRNAs: a network perspective. Curr. Top. Dev. Biol. 99:237–55 [Google Scholar]
  73. Siciliano V, Garzilli I, Fracassi C, Criscuolo S, Ventre S, di Bernardo D. 73.  2013. MiRNAs confer phenotypic robustness to gene networks by suppressing biological noise. Nat. Commun. 4:2364 [Google Scholar]
  74. Posadas DM, Carthew RW. 74.  2014. MicroRNAs and their roles in developmental canalization. Curr. Opin. Genet. Dev. 27:1–6 [Google Scholar]
  75. Ha M, Kim VN. 75.  2014. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15:509–24 [Google Scholar]
  76. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N. 76.  et al. 2005. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740–44 [Google Scholar]
  77. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. 77.  2005. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123:631–40 [Google Scholar]
  78. Wilson RC, Doudna JA. 78.  2013. Molecular mechanisms of RNA interference. Annu. Rev. Biophys. 42:217–39 [Google Scholar]
  79. Wang D, Zhang Z, O'Loughlin E, Lee T, Houel S. 79.  et al. 2012. Quantitative functions of Argonaute proteins in mammalian development.. Genes Dev 26:693–704 [Google Scholar]
  80. Meister G. 80.  2013. Argonaute proteins: functional insights and emerging roles. Nat. Rev. Genet. 14:447–59 [Google Scholar]
  81. Ma JB, Ye K, Patel DJ. 81.  2004. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 429:318–22 [Google Scholar]
  82. Elkayam E, Kuhn CD, Tocilj A, Haase AD, Greene EM. 82.  et al. 2012. The structure of human argonaute-2 in complex with miR-20a. Cell 150:100–10 [Google Scholar]
  83. Kuhn CD, Joshua-Tor L. 83.  2013. Eukaryotic Argonautes come into focus. Trends Biochem. Sci. 38:263–71 [Google Scholar]
  84. Kwak PB, Tomari Y. 84.  2012. The N domain of Argonaute drives duplex unwinding during RISC assembly. Nat. Struct. Mol. Biol. 19:145–51 [Google Scholar]
  85. Kawamata T, Seitz H, Tomari Y. 85.  2009. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat. Struct. Mol. Biol. 16:953–60 [Google Scholar]
  86. Bartel DP. 86.  2009. MicroRNAs: target recognition and regulatory functions. Cell 136:215–33 [Google Scholar]
  87. Hausser J, Zavolan M. 87.  2014. Identification and consequences of miRNA-target interactions—beyond repression of gene expression. Nat. Rev. Genet. 15:599–612 [Google Scholar]
  88. Patel DJ. 88.  2014. RNA. Complete pairing not needed. Science 346:542–43 [Google Scholar]
  89. Schirle NT, Sheu-Gruttadauria J, MacRae IJ. 89.  2014. Structural basis for microRNA targeting. Science 346:608–13 [Google Scholar]
  90. Parker JS, Parizotto EA, Wang M, Roe SM, Barford D. 90.  2009. Enhancement of the seed-target recognition step in RNA silencing by a PIWI/MID domain protein. Mol. Cell 33:204–14 [Google Scholar]
  91. Helwak A, Kudla G, Dudnakova T, Tollervey D. 91.  2013. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153:654–65 [Google Scholar]
  92. Agarwal V, Bell GW, Nam JW, Bartel DP. 92.  2015. Predicting effective microRNA target sites in mammalian mRNAs. eLife 4:e05005 [Google Scholar]
  93. Huntzinger E, Izaurralde E. 93.  2011. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat. Rev. Genet. 12:99–110 [Google Scholar]
  94. Fabian MR, Mathonnet G, Sundermeier T, Mathys H, Zipprich JT. 94.  et al. 2009. Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Mol. Cell 35:868–80 [Google Scholar]
  95. Huntzinger E, Kuzuoglu-Ozturk D, Braun JE, Eulalio A, Wohlbold L, Izaurralde E. 95.  2013. The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets. Nucleic Acids Res. 41:978–94 [Google Scholar]
  96. Braun JE, Huntzinger E, Izaurralde E. 96.  2012. A molecular link between miRISCs and deadenylases provides new insight into the mechanism of gene silencing by microRNAs. Cold Spring Harb. Perspect. Biol. 4:12 [Google Scholar]
  97. Fabian MR, Sonenberg N, Filipowicz W. 97.  2010. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 79:351–79 [Google Scholar]
  98. Eichhorn SW, Guo H, McGeary SE, Rodriguez-Mias RA, Shin C. 98.  et al. 2014. mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol. Cell 56:104–15 [Google Scholar]
  99. Tay Y, Rinn J, Pandolfi PP. 99.  2014. The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344–52 [Google Scholar]
  100. Yuan Y, Liu B, Xie P, Zhang MQ, Li Y. 100.  et al. 2015. Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit. PNAS 112:3158–63 [Google Scholar]
  101. Bosson AD, Zamudio JR, Sharp PA. 101.  2014. Endogenous miRNA and target concentrations determine susceptibility to potential ceRNA competition. Mol. Cell 56:347–59 [Google Scholar]
  102. Shu J, Xia Z, Li L, Liang ET, Slipek N. 102.  et al. 2012. Dose-dependent differential mRNA target selection and regulation by let-7a-7f and miR-17–92 cluster microRNAs. RNA Biol. 9:1275–87 [Google Scholar]
  103. Gantier MP, McCoy CE, Rusinova I, Saulep D, Wang D. 103.  et al. 2011. Analysis of microRNA turnover in mammalian cells following Dicer1 ablation. Nucleic Acids Res. 39:5692–703 [Google Scholar]
  104. Winter J, Diederichs S. 104.  2011. Argonaute proteins regulate microRNA stability: increased microRNA abundance by Argonaute proteins is due to microRNA stabilization. RNA Biol. 8:1149–57 [Google Scholar]
  105. Guo Y, Liu J, Elfenbein SJ, Ma Y, Zhong M. 105.  et al. 2015. Characterization of the mammalian miRNA turnover landscape. Nucleic Acids Res. 43:2326–41 [Google Scholar]
  106. Schaefer A, O'Carroll D, Tan CL, Hillman D, Sugimori M. 106.  et al. 2007. Cerebellar neurodegeneration in the absence of microRNAs. J. Exp. Med. 204:1553–58 [Google Scholar]
  107. Hock J, Weinmann L, Ender C, Rudel S, Kremmer E. 107.  et al. 2007. Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. EMBO Rep. 8:1052–60 [Google Scholar]
  108. La Rocca G, Olejniczak SH, Gonzalez AJ, Briskin D, Vidigal JA. 108.  et al. 2015. In vivo, Argonaute-bound microRNAs exist predominantly in a reservoir of low molecular weight complexes not associated with mRNA. PNAS 112:767–72 [Google Scholar]
  109. Olejniczak SH, La Rocca G, Gruber JJ, Thompson CB. 109.  2013. Long-lived microRNA-Argonaute complexes in quiescent cells can be activated to regulate mitogenic responses. PNAS 110:157–62 [Google Scholar]
  110. Gibbings D, Mostowy S, Jay F, Schwab Y, Cossart P, Voinnet O. 110.  2012. Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nat. Cell Biol. 14:1314–21 [Google Scholar]
  111. Ghosh S, Bose M, Ray A, Bhattacharyya SN. 111.  2015. Polysome arrest restricts miRNA turnover by preventing exosomal export of miRNA in growth-retarded mammalian cells. Mol. Biol. Cell 26:1072–83 [Google Scholar]
  112. Gibbings D, Leblanc P, Jay F, Pontier D, Michel F. 112.  et al. 2012. Human prion protein binds Argonaute and promotes accumulation of microRNA effector complexes. Nat. Struct. Mol. Biol. 19:517–24 S1 [Google Scholar]
  113. Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. 113.  2009. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell Biol. 11:1143–49 [Google Scholar]
  114. Li L, Zhu D, Huang L, Zhang J, Bian Z. 114.  et al. 2012. Argonaute 2 complexes selectively protect the circulating microRNAs in cell-secreted microvesicles. PLOS ONE 7:e46957 [Google Scholar]
  115. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. 115.  2010. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285:17442–52 [Google Scholar]
  116. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. 116.  2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:654–59 [Google Scholar]
  117. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ. 117.  et al. 2008. Detection of microRNA expression in human peripheral blood microvesicles. PLOS ONE 3:e3694 [Google Scholar]
  118. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD. 118.  et al. 2014. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 8:1432–46 [Google Scholar]
  119. Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F, Perez-Hernandez D, Vazquez J. 119.  et al. 2013. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4:2980 [Google Scholar]
  120. Tian T, Zhu YL, Zhou YY, Liang GF, Wang YY. 120.  et al. 2014. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery. J. Biol. Chem. 289:22258–67 [Google Scholar]
  121. Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC. 121.  et al. 2011. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. PNAS 108:5003–8 [Google Scholar]
  122. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM. 122.  et al. 2004. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–41 [Google Scholar]
  123. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ. 123.  2010. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465:584–89 [Google Scholar]
  124. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H. 124.  et al. 2003. Dicer is essential for mouse development. Nat. Genet. 35:215–17 [Google Scholar]
  125. Huang TC, Sahasrabuddhe NA, Kim MS, Getnet D, Yang Y. 125.  et al. 2012. Regulation of lipid metabolism by Dicer revealed through SILAC mice. J. Proteome Res. 11:2193–205 [Google Scholar]
  126. Melkman-Zehavi T, Oren R, Kredo-Russo S, Shapira T, Mandelbaum AD. 126.  et al. 2011. miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors. EMBO J. 30:835–45 [Google Scholar]
  127. da Costa Martins PA, Bourajjaj M, Gladka M, Kortland M, van Oort RJ. 127.  et al. 2008. Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation 118:1567–76 [Google Scholar]
  128. Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S. 128.  et al. 2012. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 16:336–47 [Google Scholar]
  129. Albinsson S, Suarez Y, Skoura A, Offermanns S, Miano JM, Sessa WC. 129.  2010. MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler. Thromb. Vasc. Biol. 30:1118–26 [Google Scholar]
  130. Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernandez-Hernando C. 130.  et al. 2011. Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. PLOS ONE 6:e18869 [Google Scholar]
  131. Sissons JR, Peschon JJ, Schmitz F, Suen R, Gilchrist M, Aderem A. 131.  2012. Cutting edge: microRNA regulation of macrophage fusion into multinucleated giant cells. J. Immunol. 189:23–27 [Google Scholar]
  132. Gantier MP, Stunden HJ, McCoy CE, Behlke MA, Wang D. 132.  et al. 2012. A miR-19 regulon that controls NF-κB signaling. Nucleic Acids Res. 40:8048–58 [Google Scholar]
  133. Voellenkle C, Rooij J, Guffanti A, Brini E, Fasanaro P. 133.  et al. 2012. Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs. RNA 18:472–84 [Google Scholar]
  134. Suarez Y, Fernandez-Hernando C, Yu J, Gerber SA, Harrison KD. 134.  et al. 2008. Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. PNAS 105:14082–87 [Google Scholar]
  135. Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC. 135.  2007. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ. Res. 100:1164–73 [Google Scholar]
  136. Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. 136.  2007. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ. Res. 101:59–68 [Google Scholar]
  137. Wu W, Xiao H, Laguna-Fernandez A, Villarreal G Jr, Wang KC. 137.  et al. 2011. Flow-dependent regulation of kruppel-like factor 2 is mediated by MicroRNA-92a. Circulation 124:633–41 [Google Scholar]
  138. Feng Y, Zhang X, Graves P, Zeng Y. 138.  2012. A comprehensive analysis of precursor microRNA cleavage by human Dicer. RNA 18:2083–92 [Google Scholar]
  139. Civelek M, Manduchi E, Riley RJ, Stoeckert CJ Jr, Davies PF. 139.  2009. Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ. Res. 105:453–61 [Google Scholar]
  140. Chaudhury H, Zakkar M, Boyle J, Cuhlmann S, van der Heiden K. 140.  et al. 2010. c-Jun N-terminal kinase primes endothelial cells at atheroprone sites for apoptosis. Arterioscler. Thromb. Vasc. Biol. 30:546–53 [Google Scholar]
  141. Shay-Salit A, Shushy M, Wolfovitz E, Yahav H, Breviario F. 141.  et al. 2002. VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells. PNAS 99:9462–67 [Google Scholar]
  142. Fernandez-Hernando C, Ackah E, Yu J, Suarez Y, Murata T. 142.  et al. 2007. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Cell Metab. 6:446–57 [Google Scholar]
  143. Hong D, Bai YP, Gao HC, Wang X, Li LF. 143.  et al. 2014. Ox-LDL induces endothelial cell apoptosis via the LOX-1-dependent endoplasmic reticulum stress pathway. Atherosclerosis 235:310–17 [Google Scholar]
  144. Peng N, Meng N, Wang S, Zhao F, Zhao J. 144.  et al. 2014. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E−/− mice. Sci. Rep. 4:5519 [Google Scholar]
  145. Akhmedov A, Rozenberg I, Paneni F, Camici GG, Shi Y. 145.  et al. 2014. Endothelial overexpression of LOX-1 increases plaque formation and promotes atherosclerosis in vivo. Eur. Heart J. 35:2839–48 [Google Scholar]
  146. Roush S, Slack FJ. 146.  2008. The let-7 family of microRNAs. Trends Cell Biol. 18:505–16 [Google Scholar]
  147. Wang Z, Lin S, Li JJ, Xu Z, Yao H. 147.  et al. 2011. MYC protein inhibits transcription of the microRNA cluster MC-let-7a-1∼let-7d via noncanonical E-box. J. Biol. Chem. 286:39703–14 [Google Scholar]
  148. Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N. 148.  et al. 2007. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–14 [Google Scholar]
  149. Wang Y, Hu X, Greshock J, Shen L, Yang X. 149.  et al. 2012. Genomic DNA copy-number alterations of the let-7 family in human cancers. PLOS ONE 7:e44399 [Google Scholar]
  150. Bao MH, Zhang YW, Lou XY, Cheng Y, Zhou HH. 150.  2014. Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries. PLOS ONE 9:e106540 [Google Scholar]
  151. Chen KC, Hsieh IC, Hsi E, Wang YS, Dai CY. 151.  et al. 2011. Negative feedback regulation between microRNA let-7g and the oxLDL receptor LOX-1. J. Cell Sci. 124:4115–24 [Google Scholar]
  152. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. 152.  2010. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. PNAS 107:13450–55 [Google Scholar]
  153. Qin X, Wang X, Wang Y, Tang Z, Cui Q. 153.  et al. 2010. MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cells. PNAS 107:3240–44 [Google Scholar]
  154. Liao YC, Wang YS, Guo YC, Lin WL, Chang MH, Juo SH. 154.  2014. Let-7g improves multiple endothelial functions through targeting transforming growth factor-beta and SIRT-1 signaling. J. Am. Coll. Cardiol. 63:1685–94 [Google Scholar]
  155. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P. 155.  et al. 2013. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15:978–90 [Google Scholar]
  156. Chen PY, Qin L, Barnes C, Charisse K, Yi T. 156.  et al. 2012. FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Rep. 2:1684–96 [Google Scholar]
  157. Zhang Y, Qin W, Zhang L, Wu X, Du N. 157.  et al. 2015. MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis. Sci. Rep. 5:9401 [Google Scholar]
  158. Zhu Y, Lu Y, Zhang Q, Liu JJ, Li TJ. 158.  et al. 2012. MicroRNA-26a/b and their host genes cooperate to inhibit the G1/S transition by activating the pRb protein. Nucleic Acids Res. 40:4615–25 [Google Scholar]
  159. Nichol D, Stuhlmann H. 159.  2012. EGFL7: A unique angiogenic signaling factor in vascular development and disease. Blood 119:1345–52 [Google Scholar]
  160. Wang S, Aurora AB, Johnson BA, Qi X, McAnally J. 160.  et al. 2008. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev. Cell 15:261–71 [Google Scholar]
  161. Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T. 161.  et al. 2008. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development 135:3989–93 [Google Scholar]
  162. Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ. 162.  2010. Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 30:1990–97 [Google Scholar]
  163. Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. 163.  2010. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature 464:1196–200 [Google Scholar]
  164. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ. 164.  et al. 2012. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat. Cell Biol. 14:249–56 [Google Scholar]
  165. Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF. 165.  et al. 2008. miR-126 regulates angiogenic signaling and vascular integrity. Dev. Cell 15:272–84 [Google Scholar]
  166. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. 166.  2008. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. PNAS 105:1516–21 [Google Scholar]
  167. Alexy T, Rooney K, Weber M, Gray WD, Searles CD. 167.  2014. TNF-α alters the release and transfer of microparticle-encapsulated miRNAs from endothelial cells. Physiol. Genomics 46:833–40 [Google Scholar]
  168. Sirois I, Groleau J, Pallet N, Brassard N, Hamelin K. 168.  et al. 2012. Caspase activation regulates the extracellular export of autophagic vacuoles. Autophagy 8:927–37 [Google Scholar]
  169. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L. 169.  et al. 2009. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci. Signal 2:ra81 [Google Scholar]
  170. Zhang Y, Yang P, Sun T, Li D, Xu X. 170.  et al. 2013. miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nat. Cell Biol. 15:284–94 [Google Scholar]
  171. Noels H, Zhou B, Tilstam PV, Theelen W, Li X. 171.  et al. 2014. Deficiency of endothelial CXCR4 reduces reendothelialization and enhances neointimal hyperplasia after vascular injury in atherosclerosis-prone mice. Arterioscler. Thromb. Vasc. Biol. 34:1209–20 [Google Scholar]
  172. Akhtar S, Gremse F, Kiessling F, Weber C, Schober A. 172.  2013. CXCL12 promotes the stabilization of atherosclerotic lesions mediated by smooth muscle progenitor cells in Apoe-deficient mice. Arterioscler. Thromb. Vasc. Biol. 33:679–86 [Google Scholar]
  173. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U. 173.  et al. 2010. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ. Res. 107:810–17 [Google Scholar]
  174. Jansen F, Yang X, Hoelscher M, Cattelan A, Schmitz T. 174.  et al. 2013. Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles. Circulation 128:2026–38 [Google Scholar]
  175. Zhou J, Li YS, Nguyen P, Wang KC, Weiss A. 175.  et al. 2013. Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress. Circ. Res. 113:40–51 [Google Scholar]
  176. Falix FA, Aronson DC, Lamers WH, Gaemers IC. 176.  2012. Possible roles of DLK1 in the Notch pathway during development and disease. Biochim. Biophys. Acta 1822:988–95 [Google Scholar]
  177. Sul HS. 177.  2009. Minireview: Pref-1: role in adipogenesis and mesenchymal cell fate. Mol. Endocrinol. 23:1717–25 [Google Scholar]
  178. Mortensen SB, Jensen CH, Schneider M, Thomassen M, Kruse TA. 178.  et al. 2012. Membrane-tethered delta-like 1 homolog (DLK1) restricts adipose tissue size by inhibiting preadipocyte proliferation. Diabetes 61:2814–22 [Google Scholar]
  179. Rodriguez P, Higueras MA, Gonzalez-Rajal A, Alfranca A, Fierro-Fernandez M. 179.  et al. 2012. The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis. Cardiovasc. Res. 93:232–41 [Google Scholar]
  180. Lakatta EG, Levy D. 180.  2003. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 107:139–46 [Google Scholar]
  181. He J, Kallin EM, Tsukada Y, Zhang Y. 181.  2008. The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b). Nat. Struct. Mol. Biol. 15:1169–75 [Google Scholar]
  182. Campisi J. 182.  2013. Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75:685–705 [Google Scholar]
  183. Yoshida Y, Hayashi Y, Suda M, Tateno K, Okada S. 183.  et al. 2014. Notch signaling regulates the lifespan of vascular endothelial cells via a p16-dependent pathway. PLOS ONE 9:e100359 [Google Scholar]
  184. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I. 184.  2002. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 105:1541–44 [Google Scholar]
  185. Warboys CM, de Luca A, Amini N, Luong L, Duckles H. 185.  et al. 2014. Disturbed flow promotes endothelial senescence via a p53-dependent pathway. Arterioscler. Thromb. Vasc. Biol. 34:985–95 [Google Scholar]
  186. Hermeking H. 186.  2010. The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–99 [Google Scholar]
  187. Ito T, Yagi S, Yamakuchi M. 187.  2010. MicroRNA-34a regulation of endothelial senescence. Biochem. Biophys. Res. Commun. 398:735–40 [Google Scholar]
  188. Fan W, Fang R, Wu X, Liu J, Feng M. 188.  et al. 2015. Shear-sensitive microRNA-34a modulates flow-dependent regulation of endothelial inflammation. J. Cell Sci. 128:70–80 [Google Scholar]
  189. Zu Y, Liu L, Lee MY, Xu C, Liang Y. 189.  et al. 2010. SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circ. Res. 106:1384–93 [Google Scholar]
  190. Hasegawa Y, Saito T, Ogihara T, Ishigaki Y, Yamada T. 190.  et al. 2012. Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans. Circulation 125:1122–33 [Google Scholar]
  191. Yamakuchi M, Ferlito M, Lowenstein CJ. 191.  2008. miR-34a repression of SIRT1 regulates apoptosis. PNAS 105:13421–26 [Google Scholar]
  192. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W. 192.  et al. 2008. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc. Res. 80:191–99 [Google Scholar]
  193. Raitoharju E, Lyytikainen LP, Levula M, Oksala N, Mennander A. 193.  et al. 2011. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study. Atherosclerosis 219:211–17 [Google Scholar]
  194. Nazari-Jahantigh M, Wei Y, Noels H, Akhtar S, Zhou Z. 194.  et al. 2012. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J. Clin. Investig. 122:4190–202 [Google Scholar]
  195. Olive V, Minella AC, He L. 195.  2015. Outside the coding genome, mammalian microRNAs confer structural and functional complexity. Sci. Signal 8:re2 [Google Scholar]
  196. Wu J, Bao J, Kim M, Yuan S, Tang C. 196.  et al. 2014. Two miRNA clusters, miR-34b/c and miR-449, are essential for normal brain development, motile ciliogenesis, and spermatogenesis. PNAS 111:E2851–57 [Google Scholar]
  197. Concepcion CP, Han YC, Mu P, Bonetti C, Yao E. 197.  et al. 2012. Intact p53-dependent responses in miR-34-deficient mice. PLOS Genet. 8:e1002797 [Google Scholar]
  198. Olivieri F, Lazzarini R, Recchioni R, Marcheselli F, Rippo MR. 198.  et al. 2013. MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling. Age 35:1157–72 [Google Scholar]
  199. Menghini R, Casagrande V, Cardellini M, Martelli E, Terrinoni A. 199.  et al. 2009. MicroRNA 217 modulates endothelial cell senescence via silent information regulator 1. Circulation 120:1524–32 [Google Scholar]
  200. Wang X, Li M, Wang Z, Han S, Tang X. 200.  et al. 2015. Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J. Biol. Chem. 290:3925–35 [Google Scholar]
  201. Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M. 201.  et al. 2014. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ. Res. 114:1389–97 [Google Scholar]
  202. Menghini R, Casagrande V, Marino A, Marchetti V, Cardellini M. 202.  et al. 2014. MiR-216a: a link between endothelial dysfunction and autophagy. Cell Death Dis. 5:e1029 [Google Scholar]
  203. Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. 203.  2000. The NF-κB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. PNAS 97:9052–57 [Google Scholar]
  204. SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM. 204.  et al. 2004. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J. Exp. Med. 199:1305–15 [Google Scholar]
  205. Xiao H, Lu M, Lin TY, Chen Z, Chen G. 205.  et al. 2013. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation 128:632–42 [Google Scholar]
  206. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W. 206.  et al. 2014. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31:722–33 [Google Scholar]
  207. Sun X, Icli B, Wara AK, Belkin N, He S. 207.  et al. 2012. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J. Clin. Investig. 122:1973–90 [Google Scholar]
  208. Sun X, He S, Wara AK, Icli B, Shvartz E. 208.  et al. 2014. Systemic delivery of microRNA-181b inhibits nuclear factor-κB activation, vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice. Circ. Res. 114:32–40 [Google Scholar]
  209. Chen Z, Wen L, Martin M, Hsu CY, Fang L. 209.  et al. 2015. Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a. Circulation 131:805–14 [Google Scholar]
  210. Loyer X, Potteaux S, Vion AC, Guerin CL, Boulkroun S. 210.  et al. 2014. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ. Res. 114:434–43 [Google Scholar]
  211. Fang Y, Davies PF. 211.  2012. Site-specific microRNA-92a regulation of Kruppel-like factors 4 and 2 in atherosusceptible endothelium. Arterioscler. Thromb. Vasc. Biol. 32:979–87 [Google Scholar]
  212. Mogilyansky E, Rigoutsos I. 212.  2013. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death Differ. 20:1603–14 [Google Scholar]
  213. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A. 213.  et al. 2008. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132:875–86 [Google Scholar]
  214. Han YC, Vidigal JA, Mu P, Yao E, Singh I. 214.  et al. 2015. An allelic series of miR-17 approximately 92-mutant mice uncovers functional specialization and cooperation among members of a microRNA polycistron. Nat. Genet. 47:766–75 [Google Scholar]
  215. Daniel J-M, Penzkofer D, Teske R, Dutzmann J, Koch A. 215.  et al. 2014. Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury. Cardiovasc. Res. 103:564–72 [Google Scholar]
  216. Chaulk SG, Thede GL, Kent OA, Xu Z, Gesner EM. 216.  et al. 2011. Role of pri-miRNA tertiary structure in miR-17∼92 miRNA biogenesis. RNA Biol. 8:1105–14 [Google Scholar]
  217. Akhtar S, Hartmann P, Karshovska E, Rinderknecht F-A, Subramanian P. 217.  et al. 2015. Endothelial hypoxia-inducible factor-1α promotes atherosclerosis and monocyte recruitment by upregulating miRNA-19a. Hypertension 66:1220–26 [Google Scholar]
  218. Son DJ, Kumar S, Takabe W, Woo Kim C, Ni CW. 218.  et al. 2013. The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis. Nat. Commun. 4:3000 [Google Scholar]
  219. Fessler MB, Parks JS. 219.  2011. Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling. J. Immunol. 187:1529–35 [Google Scholar]
  220. Ricote M, Valledor AF, Glass CK. 220.  2004. Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, inflammation, and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 24:230–39 [Google Scholar]
  221. Chawla A. 221.  2010. Control of macrophage activation and function by PPARs. Circ. Res. 106:1559–69 [Google Scholar]
  222. Huang SC, Everts B, Ivanova Y, O'Sullivan D, Nascimento M. 222.  et al. 2014. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat. Immunol. 15:846–55 [Google Scholar]
  223. Karunakaran D, Thrush AB, Nguyen MA, Richards L, Geoffrion M. 223.  et al. 2015. Macrophage mitochondrial energy status regulates cholesterol efflux and is enhanced by anti-miR33 in atherosclerosis. Circ. Res. 117:266–78 [Google Scholar]
  224. Ouimet M, Marcel YL. 224.  2012. Regulation of lipid droplet cholesterol efflux from macrophage foam cells. Arterioscler. Thromb. Vasc. Biol. 32:575–81 [Google Scholar]
  225. Schober A, Nazari-Jahantigh M, Weber C. 225.  2015. MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis. Nat. Rev. Cardiol. 12:361–74 [Google Scholar]
  226. Rayner KJ, Moore KJ. 226.  2014. MicroRNA control of high-density lipoprotein metabolism and function. Circ. Res. 114:183–92 [Google Scholar]
  227. Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T. 227.  et al. 2010. MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. PNAS 107:17321–26 [Google Scholar]
  228. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML. 228.  et al. 2010. MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328:1570–73 [Google Scholar]
  229. Rottiers V, Naar AM. 229.  2012. MicroRNAs in metabolism and metabolic disorders. Nat. Rev. Mol. Cell Biol. 13:239–50 [Google Scholar]
  230. Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM. 230.  et al. 2011. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature 478:404–7 [Google Scholar]
  231. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE. 231.  et al. 2011. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J. Clin. Investig. 121:2921–31 [Google Scholar]
  232. Fernandez-Hernando C, Ramirez CM, Goedeke L, Suarez Y. 232.  2013. MicroRNAs in metabolic disease. Arterioscler. Thromb. Vasc. Biol. 33:178–85 [Google Scholar]
  233. Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S. 233.  et al. 2012. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE−/− mice. J. Am. Heart Assoc. 1:e003376 [Google Scholar]
  234. Distel E, Barrett TJ, Chung K, Girgis NM, Parathath S. 234.  et al. 2014. miR33 inhibition overcomes deleterious effects of diabetes mellitus on atherosclerosis plaque regression in mice. Circ. Res. 115:759–69 [Google Scholar]
  235. Westerterp M, Bochem AE, Yvan-Charvet L, Murphy AJ, Wang N, Tall AR. 235.  2014. ATP-binding cassette transporters, atherosclerosis, and inflammation. Circ. Res. 114:157–70 [Google Scholar]
  236. Sun Y, Ishibashi M, Seimon T, Lee M, Sharma SM. 236.  et al. 2009. Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K. Circ. Res. 104:455–65 [Google Scholar]
  237. Elton TS, Selemon H, Elton SM, Parinandi NL. 237.  2013. Regulation of the MIR155 host gene in physiological and pathological processes. Gene 532:1–12 [Google Scholar]
  238. Wei Y, Nazari-Jahantigh M, Chan L, Zhu M, Heyll K. 238.  et al. 2013. The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation 127:1609–19 [Google Scholar]
  239. Wei Y, Zhu M, Corbalan-Campos J, Heyll K, Weber C, Schober A. 239.  2015. Regulation of Csf1r and Bcl6 in macrophages mediates the stage-specific effects of microRNA-155 on atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 35:796–803 [Google Scholar]
  240. Du F, Yu F, Wang Y, Hui Y, Carnevale K. 240.  et al. 2014. MicroRNA-155 deficiency results in decreased macrophage inflammation and attenuated atherogenesis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 34:759–67 [Google Scholar]
  241. Tian FJ, An LN, Wang GK, Zhu JQ, Li Q. 241.  et al. 2014. Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis. Cardiovasc. Res. 103:100–10 [Google Scholar]
  242. Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S. 242.  et al. 2009. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 31:220–31 [Google Scholar]
  243. Pankratz F, Bemtgen X, Zeiser R, Leonhardt F, Kreuzaler S. 243.  et al. 2015. MicroRNA-155 exerts cell-specific antiangiogenic but proarteriogenic effects during adaptive neovascularization. Circulation 131:1575–89 [Google Scholar]
  244. Curtis AM, Fagundes CT, Yang G, Palsson-McDermott EM, Wochal P. 244.  et al. 2015. Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. PNAS 112:7231–36 [Google Scholar]
  245. Yoshimura A, Naka T, Kubo M. 245.  2007. SOCS proteins, cytokine signalling and immune regulation. Nat. Rev. Immunol. 7:454–65 [Google Scholar]
  246. Recio C, Oguiza A, Lazaro I, Mallavia B, Egido J, Gomez-Guerrero C. 246.  2014. Suppressor of cytokine signaling 1-derived peptide inhibits Janus kinase/signal transducers and activators of transcription pathway and improves inflammation and atherosclerosis in diabetic mice. Arterioscler. Thromb. Vasc. Biol. 34:1953–60 [Google Scholar]
  247. Barish GD, Yu RT, Karunasiri M, Ocampo CB, Dixon J. 247.  et al. 2010. Bcl-6 and NF-κB cistromes mediate opposing regulation of the innate immune response. Genes Dev. 24:2760–65 [Google Scholar]
  248. Toney LM, Cattoretti G, Graf JA, Merghoub T, Pandolfi PP. 248.  et al. 2000. BCL-6 regulates chemokine gene transcription in macrophages. Nat. Immunol. 1:214–20 [Google Scholar]
  249. Barish GD, Yu RT, Karunasiri MS, Becerra D, Kim J. 249.  et al. 2012. The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis. Cell Metab. 15:554–62 [Google Scholar]
  250. Basso K, Schneider C, Shen Q, Holmes AB, Setty M. 250.  et al. 2012. BCL6 positively regulates AID and germinal center gene expression via repression of miR-155. J. Exp. Med. 209:2455–65 [Google Scholar]
  251. Sandhu SK, Volinia S, Costinean S, Galasso M, Neinast R. 251.  et al. 2012. miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Emu-miR-155 transgenic mouse model. PNAS 109:20047–52 [Google Scholar]
  252. Nakaya M, Tanaka M, Okabe Y, Hanayama R, Nagata S. 252.  2006. Opposite effects of rho family GTPases on engulfment of apoptotic cells by macrophages. J. Biol. Chem. 281:8836–42 [Google Scholar]
  253. Pixley FJ, Xiong Y, Yu RY, Sahai EA, Stanley ER, Ye BH. 253.  2005. BCL6 suppresses RhoA activity to alter macrophage morphology and motility. J. Cell Sci. 118:1873–83 [Google Scholar]
  254. Donners MM, Wolfs IM, Stoger LJ, van der Vorst EP, Pottgens CC. 254.  et al. 2012. Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice. PLOS ONE 7:e35877 [Google Scholar]
  255. O'Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD. 255.  et al. 2008. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J. Exp. Med. 205:585–94 [Google Scholar]
  256. He H, Xu J, Warren CM, Duan D, Li X. 256.  et al. 2012. Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages. Blood 120:3152–62 [Google Scholar]
  257. Di Gregoli K, Johnson JL. 257.  2012. Role of colony-stimulating factors in atherosclerosis. Curr. Opin. Lipidol. 23:412–21 [Google Scholar]
  258. Murayama T, Yokode M, Kataoka H, Imabayashi T, Yoshida H. 258.  et al. 1999. Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice. Circulation 99:1740–46 [Google Scholar]
  259. Phillips MC. 259.  2014. Molecular mechanisms of cellular cholesterol efflux. J. Biol. Chem. 289:24020–29 [Google Scholar]
  260. Nagata KO, Nakada C, Kasai RS, Kusumi A, Ueda K. 260.  2013. ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging. PNAS 110:5034–39 [Google Scholar]
  261. 261.  Deleted in proof
  262. Nielsen CB, Shomron N, Sandberg R, Hornstein E, Kitzman J, Burge CB. 262.  2007. Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. RNA 13:1894–910 [Google Scholar]
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