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Mediators of Inflammation
Volume 2014 (2014), Article ID 275867, 14 pages
http://dx.doi.org/10.1155/2014/275867
Review Article

MicroRNAs Involved in the Lipid Metabolism and Their Possible Implications for Atherosclerosis Development and Treatment

Jan Novák,1,2,3 Julie Bienertová-Vašků,3 Tomáš Kára,1 and Miroslav Novák1

1International Clinical Research Center, Department of Cardiovascular Diseases, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic
2Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A20, 625 00 Brno, Czech Republic
3Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A18, 625 00 Brno, Czech Republic

Received 15 November 2013; Revised 21 March 2014; Accepted 3 April 2014; Published 24 April 2014

Academic Editor: Jana Petrkova

Copyright © 2014 Jan Novák et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Ross, “Atherosclerosis: an inflammatory disease,” The New England Journal of Medicine, vol. 340, pp. 115–126, 1999. View at Publisher · View at Google Scholar
  2. C. J. Glueck, “Role of risk factor management in progression and regression of coronary and femoral artery atherosclerosis,” The American Journal of Cardiology, vol. 57, no. 14, pp. 35G–41G, 1986. View at Google Scholar · View at Scopus
  3. A. Al Montasir and M. H. Sadik, “Acute myocardial infarction in a 28 year man with familial hypercholesterolemia,” Indian Journal of Medical Sciences, vol. 66, pp. 78–81, 2012. View at Publisher · View at Google Scholar
  4. A. C. Goldberg, P. N. Hopkins, P. P. Toth et al., “Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association expert panel on familial hypercholesterolemia,” Journal of Clinical Lipidology, vol. 5, no. 3, pp. S1–S8, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. D. J. Rader, J. Cohen, and H. H. Hobbs, “Monogenic hypercholesterolemia: new insights in pathogenesis and treatment,” Journal of Clinical Investigation, vol. 111, no. 12, pp. 1795–1803, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. K. J. Rayner, Y. Suárez, A. Dávalos et al., “MiR-33 contributes to the regulation of cholesterol homeostasis,” Science, vol. 328, no. 5985, pp. 1570–1573, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. S. H. Najafi-Shoushtari, F. Kristo, Y. Li et al., “MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis,” Science, vol. 328, no. 5985, pp. 1566–1569, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. I. Gerin, L.-A. Clerbaux, O. Haumont et al., “Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation,” Journal of Biological Chemistry, vol. 285, no. 44, pp. 33652–33661, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. L. Goedeke, F. M. Vales-Lara, M. Fenstermaker et al., “A regulatory role for microRNA 33* in controlling lipid metabolism gene expression,” Molecular and Cellular Biology, vol. 33, pp. 2339–2352, 2013. View at Publisher · View at Google Scholar
  10. T. J. Marquart, R. M. Allen, D. S. Ory, and Á. Baldán, “MiR-33 links SREBP-2 induction to repression of sterol transporters,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 27, pp. 12228–12232, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. R. M. Allen, T. J. Marquart, C. J. Albert et al., “MiR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity,” The EMBO Molecular Medicine, vol. 4, pp. 882–895, 2012. View at Publisher · View at Google Scholar
  12. J. Krützfeldt, N. Rajewsky, R. Braich et al., “Silencing of microRNAs in vivo with 'antagomirs',” Nature, vol. 438, no. 7068, pp. 685–689, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Esau, S. Davis, S. F. Murray et al., “MiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting,” Cell Metabolism, vol. 3, no. 2, pp. 87–98, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. S. H. Hsu, B. Wang, J. Kota et al., “Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver,” The Journal of Clinical Investigation, vol. 122, pp. 2871–2883, 2012. View at Publisher · View at Google Scholar
  15. W. C. Tsai, S. D. Hsu, C. S. Hsu et al., “MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis,” The Journal of Clinical Investigation, vol. 122, pp. 2884–2897, 2012. View at Publisher · View at Google Scholar
  16. T. Shirasaki, M. Honda, T. Shimakami et al., “MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells,” Journal of Virology, vol. 87, pp. 5270–5286, 2013. View at Google Scholar
  17. K. Kida, M. Nakajima, T. Mohri et al., “PPARα is regulated by miR-21 and miR-27b in human liver,” Pharmaceutical Research, vol. 28, no. 10, pp. 2467–2476, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. K. C. Vickers, B. M. Shoucri, M. G. Levin et al., “MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia,” Hepatology, vol. 57, pp. 533–542, 2013. View at Publisher · View at Google Scholar
  19. Q. Lin, Z. Gao, R. M. Alarcon, J. Ye, and Z. Yun, “A role of miR-27 in the regulation of adipogenesis,” FEBS Journal, vol. 276, no. 8, pp. 2348–2358, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Y. Kim, A. Y. Kim, H. W. Lee et al., “MiR-27a is a negative regulator of adipocyte differentiation via suppressing PPARγ expression,” Biochemical and Biophysical Research Communications, vol. 392, no. 3, pp. 323–328, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. D. Iliopoulos, K. Drosatos, Y. Hiyama, I. J. Goldberg, and V. I. Zannis, “MicroRNA-370 controls the expression of MicroRNA-122 and Cpt1α and affects lipid metabolism,” Journal of Lipid Research, vol. 51, no. 6, pp. 1513–1523, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Q. de Aguiar Vallim, E. J. Tarling, T. Kim et al., “MicroRNA-144 regulates hepatic ATP binding cassette transporter A1 and plasma high-density lipoprotein after activation of the nuclear receptor farnesoid X receptor,” Circulation Research, vol. 112, pp. 1602–1612, 2013. View at Publisher · View at Google Scholar
  23. C. M. Ramirez, N. Rotllan, A. V. Vlassov et al., “Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144,” Circulation Research, vol. 112, pp. 1592–1601, 2013. View at Publisher · View at Google Scholar
  24. D. Zhong, G. Huang, Y. Zhang et al., “MicroRNA-1 and microRNA-206 suppress LXRalpha-induced lipogenesis in hepatocytes,” Cellular Signalling, vol. 25, pp. 1429–137, 2013. View at Publisher · View at Google Scholar
  25. J. Xu, G. Hu, M. Lu et al., “MiR-9 reduces human acyl-coenzyme A:cholesterol acyltransferase-1 to decrease THP-1 macrophage-derived foam cell formation,” Acta Biochimica et Biophysica Sinica, vol. 45, pp. 953–962, 2013. View at Publisher · View at Google Scholar
  26. P. Thulin, T. Wei, O. Werngren et al., “MicroRNA-9 regulates the expression of peroxisome proliferator-activated receptor delta in human monocytes during the inflammatory response,” International Journal of Molecular Medicine, vol. 31, pp. 1003–1010, 2013. View at Publisher · View at Google Scholar
  27. J. Ahn, H. Lee, C. H. Jung, and T. Ha, “Lycopene inhibits hepatic steatosis via microRNA-21-induced downregulation of fatty acid-binding protein 7 in mice fed a high-fat diet,” Molecular nutrition and Food Research, vol. 56, pp. 1665–1674, 2012. View at Publisher · View at Google Scholar
  28. T. Chen, Z. Li, J. Tu et al., “MicroRNA-29a regulates pro-inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL-stimulated dendritic cells,” FEBS Letters, vol. 585, no. 4, pp. 657–663, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Soh, J. Iqbal, J. Queiroz, C. Fernandez-Hernando, and M. M. Hussain, “MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion,” Nature Medicine, vol. 19, pp. 892–900, 2013. View at Publisher · View at Google Scholar
  30. T. Chen, Z. Huang, L. Wang et al., “MicroRNA-125a-5p partly regulates the inflammatory response, lipid uptake, and ORP9 expression in oxLDL-stimulated monocyte/macrophages,” Cardiovascular Research, vol. 83, no. 1, pp. 131–139, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Chen, Z. Li, T. Jing et al., “MicroRNA-155 regulates lipid uptake, adhesion/chemokine marker secretion and SCG2 expression in oxLDL-stimulated dendritic cells/macrophages,” International Journal of Cardiology, vol. 147, no. 3, pp. 446–447, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. A. M. Miller, D. S. Gilchrist, J. Nijjar et al., “MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice,” PLoS ONE, vol. 8, Article ID 0072324, 2013. View at Publisher · View at Google Scholar
  33. G. F. Zhu, L. X. Yang, R. W. Guo et al., “MiR-155 inhibits oxidized low-density lipoprotein-induced apoptosis of RAW264. 7 cells,” Molecular and Cellular Biochemistry, vol. 382, pp. 253–261, 2013. View at Publisher · View at Google Scholar
  34. X. Sun, S. He, A. K. Wara et al., “Systemic delivery of MicroRNA-181b inhibits NF-kappaB activation, vascular inflammation, and atherosclerosis in Apoe-/- Mice,” Circulation Research, vol. 114, no. 1, pp. 32–40, 2014. View at Publisher · View at Google Scholar
  35. X. Li, Y. T. Chen, S. Josson et al., “MicroRNA-185 and 342 inhibit tumorigenicity and induce apoptosis through blockade of the SREBP metabolic pathway in prostate cancer cells,” PLoS ONE, vol. 8, Article ID e70987, 2013. View at Publisher · View at Google Scholar
  36. H. Yin, M. Hu, R. Zhang, Z. Shen, L. Flatow, and M. You, “MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down-regulating SIRT1,” Journal of Biological Chemistry, vol. 287, no. 13, pp. 9817–9826, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Nakanishi, Y. Nakagawa, N. Tokushige et al., “The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice,” Biochemical and Biophysical Research Communications, vol. 385, no. 4, pp. 492–496, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Carrer, N. Liu, C. E. Grueter et al., “Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, pp. 15330–15335, 2012. View at Publisher · View at Google Scholar
  39. I. Gerin, G. T. Bommer, C. S. McCoin, K. M. Sousa, V. Krishnan, and O. A. MacDougald, “Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis,” The American Journal of Physiology: Endocrinology and Metabolism, vol. 299, no. 2, pp. E198–E206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Ahn, H. Lee, C. H. Chung, and T. Ha, “High fat diet induced downregulation of microRNA-467b increased lipoprotein lipase in hepatic steatosis,” Biochemical and Biophysical Research Communications, vol. 414, no. 4, pp. 664–669, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. G. P. Tian, W. J. Chen, P. P. He et al., “MicroRNA-467b targets LPL gene in RAW 264. 7 macrophages and attenuates lipid accumulation and proinflammatory cytokine secretion,” Biochimie, vol. 94, pp. 2749–2755, 2012. View at Publisher · View at Google Scholar
  42. D. Zhong, Y. Zhang, Y. J. Zeng et al., “MicroRNA-613 represses lipogenesis in HepG2 cells by downregulating LXRalpha,” Lipids in Health and Disease, vol. 12, article 32, 2013. View at Publisher · View at Google Scholar
  43. E. Ginter and V. Simko, “New promising potential in fighting atherosclerosis: HDL and reverse cholesterol transport,” Bratislavske Lekarske Listy, vol. 114, pp. 172–176, 2013. View at Google Scholar
  44. I. Peluso, G. Morabito, L. Urban, F. Ioannone, and M. Serafini, “Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst,” Endocrine, Metabolic and Immune Disorders Drug Targets, vol. 12, pp. 351–360, 2012. View at Google Scholar
  45. H. C. McGill Jr., C. A. McMahan, A. W. Kruski, and G. E. Mott, “Relationship of lipoprotein cholesterol concentrations to experimental atherosclerosis in baboons,” Arteriosclerosis, vol. 1, no. 1, pp. 3–12, 1981. View at Google Scholar · View at Scopus
  46. H. Shimano, H. Aburatani, N. Mori et al., “Down-regulation of hepatic LDL receptor protein and messenger RNA in fasted rabbits,” Journal of Biochemistry, vol. 104, no. 5, pp. 712–716, 1988. View at Google Scholar · View at Scopus
  47. J. Kzhyshkowska, C. Neyen, and S. Gordon, “Role of macrophage scavenger receptors in atherosclerosis,” Immunobiology, vol. 217, no. 5, pp. 492–502, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. Y. Lee, K. Jeon, J.-T. Lee, S. Kim, and V. N. Kim, “MicroRNA maturation: stepwise processing and subcellular localization,” The EMBO Journal, vol. 21, no. 17, pp. 4663–4670, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. L. He and G. J. Hannon, “MicroRNAs: small RNAs with a big role in gene regulation,” Nature Reviews Genetics, vol. 5, pp. 522–531, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Madrigal-Matute, N. Rotllan, J. F. Aranda, and C. Fernandez-Hernando, “MicroRNAs and atherosclerosis,” Current Atherosclerosis Reports, vol. 15, no. 5, article 322, 2013. View at Publisher · View at Google Scholar
  51. J.-S. Yang and E. C. Lai, “Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants,” Molecular Cell, vol. 43, no. 6, pp. 892–903, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. P. S. Mitchell, R. K. Parkin, E. M. Kroh et al., “Circulating microRNAs as stable blood-based markers for cancer detection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 30, pp. 10513–10518, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. K. C. Vickers, B. T. Palmisano, B. M. Shoucri, R. D. Shamburek, and A. T. Remaley, “MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins,” Nature Cell Biology, vol. 13, no. 4, pp. 423–435, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Redova, J. Sana, and O. Slaby, “Circulating miRNAs as new blood-based biomarkers for solid cancers,” Future Oncology, vol. 9, pp. 387–402, 2013. View at Publisher · View at Google Scholar
  55. G. Musso, R. Gambino, and M. Cassader, “Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis,” Progress in Lipid Research, vol. 52, pp. 175–91, 2013. View at Publisher · View at Google Scholar
  56. A. Rodriguez, S. Griffiths-Jones, J. L. Ashurst, and A. Bradley, “Identification of mammalian microRNA host genes and transcription units,” Genome Research, vol. 14, pp. 1902–1910, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Kozomara and S. Griffiths-Jones, “MiRBase: integrating microRNA annotation and deep-sequencing data,” Nucleic Acids Research, vol. 39, no. 1, pp. D152–D157, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Dávalos, L. Goedeke, P. Smibert et al., “MiR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 22, pp. 9232–9237, 2011. View at Publisher · View at Google Scholar · View at Scopus
  59. C. M. Ramirez, L. Goedeke, N. Rotllan et al., “MicroRNA 33 regulates glucose metabolism,” Molecular and Cellular Biology, vol. 33, pp. 2891–2902, 2013. View at Publisher · View at Google Scholar
  60. M. Lagos-Quintana, R. Rauhut, A. Yalcin, J. Meyer, W. Lendeckel, and T. Tuschl, “Identification of tissue-specific MicroRNAs from mouse,” Current Biology, vol. 12, no. 9, pp. 735–739, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. J. Chang, E. Nicolas, D. Marks et al., “MiR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1,” RNA Biology, vol. 1, no. 2, pp. 106–113, 2004. View at Google Scholar · View at Scopus
  62. K. D. Conrad and M. Niepmann, “Role of microRNAs in hepatitis C virus RNA replication,” Archives of Virology, 2013. View at Publisher · View at Google Scholar
  63. J. Hu, Y. Xu, J. Hao, S. Wang, C. Li, and S. Meng, “MiR-122 in hepatic function and liver diseases,” Protein and Cell, vol. 3, pp. 364–371, 2012. View at Publisher · View at Google Scholar
  64. J. Elmén, M. Lindow, A. Silahtaroglu et al., “Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver,” Nucleic Acids Research, vol. 36, no. 4, pp. 1153–1162, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. K. J. Moore, K. J. Rayner, Y. Suárez, and C. Fernández-Hernando, “MicroRNAs and cholesterol metabolism,” Trends in Endocrinology and Metabolism, vol. 21, no. 12, pp. 699–706, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. W. Gao, H. W. He, Z. M. Wang et al., “Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease,” Lipids in Health and Disease, vol. 11, artricle 55, 2012. View at Publisher · View at Google Scholar
  67. K. C. Vickers and D. J. Rader, “Nuclear receptors and microRNA-144 coordinately regulate cholesterol efflux,” Circulation Research, vol. 112, pp. 1529–1531, 2013. View at Publisher · View at Google Scholar
  68. D. Wang, M. Xia, X. Yan et al., “Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b,” Circulation Research, vol. 111, Article ID 266502, pp. 967–981, 2012. View at Google Scholar
  69. D. Sun, J. Zhang, J. Xie, W. Wei, M. Chen, and X. Zhao, “MiR-26 controls LXR-dependent cholesterol efflux by targeting ABCA1 and ARL7,” FEBS Letters, vol. 586, pp. 1472–1479, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. M. H. Kang, L. Zhang, N. Wijesekara et al., “Regulation of ABCA1 protein expression and function in hepatic and pancreatic islet cells by miR-145,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 12, pp. 2724–2732, 2013. View at Publisher · View at Google Scholar
  71. J. Kim, H. Yoon, C. M. Ramírez et al., “MiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression,” Experimental Neurology, vol. 235, no. 2, pp. 476–483, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. C. M. Ramirez, A. Dávalos, L. Goedeke et al., “MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 11, pp. 2707–2714, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. J. E. Fish, M. M. Santoro, S. U. Morton et al., “MiR-126 regulates angiogenic signaling and vascular integrity,” Developmental Cell, vol. 15, no. 2, pp. 272–284, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Wang, A. B. Aurora, B. A. Johnson et al., “The endothelial-specific MicroRNA miR-126 governs vascular integrity and angiogenesis,” Developmental Cell, vol. 15, no. 2, pp. 261–271, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Li, Y. Zhang, Y. Liu et al., “Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis,” The Journal of Biological Chemistry, vol. 288, pp. 23586–23596, 2013. View at Publisher · View at Google Scholar
  76. Y. Zhang, D. Liu, X. Chen et al., “Secreted monocytic miR-150 enhances targeted endothelial cell migration. Molecular cell,” vol. 39, pp. 133–144, 2010. View at Publisher · View at Google Scholar
  77. J. Wagner, M. Riwanto, C. Besler et al., “Characterization of levels and cellular transfer of circulating lipoprotein-bound microRNAs,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, Article ID 300741, pp. 1392–1400, 2013. View at Google Scholar
  78. J. A. Weber, D. H. Baxter, S. Zhang et al., “The microRNA spectrum in 12 body fluids,” Clinical Chemistry, vol. 56, no. 11, pp. 1733–1741, 2010. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee, and J. O. Lötvall, “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,” Nature Cell Biology, vol. 9, no. 6, pp. 654–659, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. M. P. Hunter, N. Ismail, X. Zhang et al., “Detection of microRNA expression in human peripheral blood microvesicles,” PLoS ONE, vol. 3, no. 11, Article ID e3694, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Zernecke, K. Bidzhekov, H. Noels et al., “Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection,” Science Signaling, vol. 2, no. 100, Article ID ra81, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Turchinovich, L. Weiz, A. Langheinz, and B. Burwinkel, “Characterization of extracellular circulating microRNA,” Nucleic Acids Research, vol. 39, no. 16, pp. 7223–7233, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. X. Ji, R. Takahashi, Y. Hiura, G. Hirokawa, Y. Fukushima, and N. Iwai, “Plasma miR-208 as a biomarker of myocardial injury,” Clinical Chemistry, vol. 55, no. 11, pp. 1944–1949, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. N. Kosaka, H. Iguchi, Y. Yoshioka, F. Takeshita, Y. Matsuki, and T. Ochiya, “Secretory mechanisms and intercellular transfer of microRNAs in living cells,” Journal of Biological Chemistry, vol. 285, no. 23, pp. 17442–17452, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. P. Diehl, A. Fricke, L. Sander et al., “Microparticles: major transport vehicles for distinct microRNAs in circulation,” Cardiovascular Research, vol. 93, no. 4, pp. 633–644, 2012. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Fichtlscherer, S. De Rosa, H. Fox et al., “Circulating microRNAs in patients with coronary artery disease,” Circulation Research, vol. 107, no. 5, pp. 677–684, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. D. S. Karolina, S. Tavintharan, A. Armugam et al., “Circulating miRNA profiles in patients with metabolic syndrome,” The Journal of Clinical Endocrinology and Metabolism, vol. 97, pp. 2271–2276, 2012. View at Publisher · View at Google Scholar
  88. N. A. Finn, D. Eapen, P. Manocha et al., “Coronary heart disease alters intercellular communication by modifying microparticle-mediated microRNA transport,” FEBS Letters, vol. 587, pp. 3456–3463, 2013. View at Publisher · View at Google Scholar
  89. J. Zhou, Y. S. Li, P. Nguyen et al., “Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress,” Circulation Research, vol. 113, pp. 40–51, 2013. View at Publisher · View at Google Scholar
  90. X. Sun, M. Zhang, A. Sanagawa et al., “Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol,” Thrombosis Journal, vol. 10, article 16, 2012. View at Publisher · View at Google Scholar
  91. T. A. Harris, M. Yamakuchi, M. Ferlito, J. T. Mendell, and C. J. Lowenstein, “MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 5, pp. 1516–1521, 2008. View at Publisher · View at Google Scholar · View at Scopus
  92. A. Zampetaki, P. Willeit, L. Tilling et al., “Prospective study on circulating MicroRNAs and risk of myocardial infarction,” Journal of the American College of Cardiology, vol. 60, pp. 290–299, 2012. View at Publisher · View at Google Scholar
  93. H. Q. Lu, C. Liang, Z. Q. He, M. Fan, and Z. G. Wu, “Circulating miR-214 is associated with the severity of coronary artery disease,” Journal of Geriatric Cardiology, vol. 10, pp. 34–38, 2013. View at Publisher · View at Google Scholar
  94. P. C. Tsai, Y. C. Liao, Y. S. Wang, H. F. Lin, R. T. Lin, and S. H. Juo, “Serum microRNA-21 and microRNA-221 as potential biomarkers for cerebrovascular disease,” Journal of Vascular Research, vol. 50, pp. 346–354, 2013. View at Publisher · View at Google Scholar
  95. H. Lu, R. J. Buchan, and S. A. Cook, “MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism,” Cardiovascular Research, vol. 86, no. 3, pp. 410–420, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. L. Wang, X. J. Jia, H. J. Jiang et al., “MicroRNAs 185, 96, and 223 repress selective high-density lipoprotein cholesterol uptake through posttranscriptional inhibition,” Molecular and Cellular Biology, vol. 33, pp. 1956–1964, 2013. View at Publisher · View at Google Scholar
  97. F. Bauernfeind, A. Rieger, F. A. Schildberg, P. A. Knolle, J. L. Schmid-Burgk, and V. Hornung, “NLRP3 inflammasome activity is negatively controlled by miR-223,” Journal of Immunology, vol. 189, pp. 4175–4181, 2012. View at Publisher · View at Google Scholar
  98. F. Tabet, K. C. Vickers, L. F. Cuesta Torres et al., “HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells,” Nature Communications, vol. 5, Article ID 3292, 2014. View at Publisher · View at Google Scholar
  99. D. Duffy and D. J. Rader, “Update on strategies to increase HDL quantity and function,” Nature Reviews Cardiology, vol. 6, pp. 455–463, 2009. View at Publisher · View at Google Scholar
  100. M. Haneklaus, M. Gerlic, O. 'Neill LA, and S. L. Masters, “MiR-223: infection, inflammation and cancer,” Journal of Internal Medicine, vol. 274, pp. 215–226, 2013. View at Publisher · View at Google Scholar
  101. X. Ma, C. Ma, and X. zheng, “MicroRNA-155 in the pathogenesis of atherosclerosis: a conflicting role?” Heart, Lung and Circulation, vol. 22, pp. 811–818, 2013. View at Publisher · View at Google Scholar
  102. T. R. Pedersen, “Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S),” The Lancet, vol. 344, no. 8934, pp. 1383–1389, 1994. View at Google Scholar · View at Scopus
  103. A. Soriano, L. Jubierre, A. Almazan-Moga et al., “MicroRNAs as pharmacological targets in cancer,” Pharmacological Research, vol. 75, pp. 3–14, 2013. View at Publisher · View at Google Scholar
  104. T. J. Marquart, J. Wu, A. J. Lusis, and A. Baldan, “Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, pp. 455–458, 2013. View at Publisher · View at Google Scholar
  105. N. Rotllan, C. M. Ramirez, B. Aryal, C. C. Esau, and C. Fernandez-Hernando, “Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice: brief report,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, pp. 1973–1977, 2013. View at Publisher · View at Google Scholar
  106. T. Horie, O. Baba, Y. Kuwabara et al., “MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE-/- mice,” Journal of the American Heart Association, vol. 1, Article ID e003376, 2012. View at Publisher · View at Google Scholar
  107. K. J. Rayner, C. C. Esau, F. N. Hussain et al., “Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides,” Nature, vol. 478, no. 7369, pp. 404–407, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. K. J. Rayner, F. J. Sheedy, C. C. Esau et al., “Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis,” Journal of Clinical Investigation, vol. 121, no. 7, pp. 2921–2931, 2011. View at Publisher · View at Google Scholar · View at Scopus
  109. http://www.regulusrx.com/therapeutic-areas/#Atherosclerosis.
  110. E. S. Hildebrandt-Eriksen, V. Aarup, R. Persson, H. F. Hansen, M. E. Munk, and H. Orum, “A locked nucleic acid oligonucleotide targeting microRNA 122 is well-tolerated in cynomolgus monkeys,” Nucleic Acid Therapeutics, vol. 22, pp. 152–161, 2012. View at Publisher · View at Google Scholar