Unlocking the Door to New Therapies in Cardiovascular Disease: MicroRNAs Hold the Key

Current Cardiology Reports

Volumn 16, Issue 11, 2014, Pages 1-12

  Nguyen, My Anh ^a   Karunakaran, Denuja ^a   Rayner, Katey J ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

Author keywords

Atherosclerosis; miRNA; Myocardium; Therapeutic

Indexed keywords

ANTAGOMIR; CARDIOVASCULAR AGENT; MICRORNA; MICRORNA 1; MICRORNA 107; MICRORNA 126; MICRORNA 133A; MICRORNA 133B; MICRORNA 135A; MICRORNA 139; MICRORNA 142 5P; MICRORNA 144 ANTAGONIST; MICRORNA 145; MICRORNA 147; MICRORNA 155; MICRORNA 17; MICRORNA 18B; MICRORNA 195; MICRORNA 208A; MICRORNA 208A INHIBITOR; MICRORNA 208B; MICRORNA 21 INHIBITOR; MICRORNA 22; MICRORNA 30A; MICRORNA 423 5P; MICRORNA 499; MICRORNA 499 5P; MICRORNA 92A; MIRAVIRSEN; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANGIOGENIC FACTOR; BIOLOGICAL MARKER;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDITIS; CELL PROLIFERATION; DISEASE ASSOCIATION; DRUG MECHANISM; DRUG TARGETING; EXTRACELLULAR MATRIX; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; NONHUMAN; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; CARDIOMEGALY; CARDIOVASCULAR DISEASES; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HEART MUSCLE; HEART VENTRICLE REMODELING; METABOLISM; MOLECULARLY TARGETED THERAPY; RNA PROCESSING; TRENDS;

ANGIOGENESIS INDUCING AGENTS; ATHEROSCLEROSIS; BIOLOGICAL MARKERS; CARDIOMEGALY; CARDIOVASCULAR DISEASES; GENE EXPRESSION REGULATION; HUMANS; HYPERLIPIDEMIAS; MICRORNAS; MOLECULAR TARGETED THERAPY; MYOCARDIUM; RNA PROCESSING, POST-TRANSCRIPTIONAL; VENTRICULAR REMODELING;

EID: 84910598089     PISSN: 15233782     EISSN: 15343170     Source Type: Journal    
DOI: 10.1007/s11886-014-0539-7     Document Type: Review

References (95)

1. Chilton RJ. Pathophysiology of coronary heart disease: a brief review. J Am Osteopath Assoc. 2004;104(9 Suppl 7):S5–8.
2. Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81. doi:10.1016/S0140-6736(10)61350-5.
3. Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, Segal E. Genomics: ENCODE explained. Nature. 2012;489(7414):52–5. doi:10.1038/489052a.
4. Hata A. Functions of microRNAs in cardiovascular biology and disease. Annu Rev Physiol. 2013;75:69–93. doi:10.1146/annurev-physiol-030212-183737.
5. Condorelli G, Latronico MVG, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol. 2014;63(21):2177–87. doi:10.1016/j.jacc.2014.01.050.
6. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3):341–55. doi:10.1016/j.cell.2011.04.005.
7. Feig JE. Regression of atherosclerosis: insights from animal and clinical studies. Ann Glob Health. 2014;80(1):13–23. doi:10.1016/j.aogh.2013.12.001.
8. Najafi-Shoushtari SH, Kristo F, Li Y, Shioda T, Cohen DE, Gerszten RE, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328(5985):1566–9. doi:10.1126/science.1189123.
9. Rayner KJ, Suarez Y, Davalos A, Parathath S, Fitzgerald ML, Tamehiro N, et al. MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010;328(5985):1570–3. doi:10.1126/science.1189862.
10. Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285(44):33652–61. doi:10.1074/jbc.M110.152090.
11. Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, et al. MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo. Proc Natl Acad Sci U S A. 2010;107(40):17321–6. doi:10.1073/pnas.1008499107.
12. Marquart TJ, Allen RM, Ory DS, Baldan A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A. 2010;107(27):12228–32. doi:10.1073/pnas.1005191107.
13. Rayner KJ, Sheedy FJ, Esau CC, Hussain FN, Temel RE, Parathath S, et al. Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis. J Clin Invest. 2011;121(7):2921–31. doi:10.1172/jci57275.
14. Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, et al. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE-/- mice. J Am Heart Assoc. 2012;1(6):e003376. doi:10.1161/JAHA.112.003376.
15. Rotllan N, Ramirez CM, Aryal B, Esau CC, Fernandez-Hernando C. Therapeutic silencing of MicroRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice. Arterioscler, Thromb, Vasc Biol. 2013. doi:10.1161/ATVBAHA.113.301732.
16. Rayner KJ, Esau CC, Hussain FN, McDaniel AL, Marshall SM, van Gils JM, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011;478(7369):404–7. doi:10.1038/nature10486.
17. de Aguiar Vallim TQ, Tarling EJ, Kim T, Civelek M, Baldan A, Esau C, 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. Circ Res. 2013;112(12):1602–12. doi:10.1161/CIRCRESAHA.112.300648.
18. Ramirez CM, Rotllan N, Vlassov AV, Davalos A, Li M, Goedeke L, et al. Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circ Res. 2013;112(12):1592–601. doi:10.1161/CIRCRESAHA.112.300626.
19. Ramirez CM, Davalos A, Goedeke L, Salerno AG, Warrier N, Cirera-Salinas D, et al. MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1. Arterioscler, Thromb, Vasc Biol. 2011;31(11):2707–14. doi:10.1161/ATVBAHA.111.232066.
20. Hu Y-W, Hu Y-R, Zhao J-Y, Li S-F, Ma X, Wu S-G, et al. An agomir of miR-144-3p accelerates plaque formation through impairing reverse cholesterol transport and promoting pro-inflammatory cytokine production. PLoS One. 2014;9(4):e94997. doi:10.1371/journal.pone.0094997.
21. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12(9):735–9. doi:10.1016/S0960-9822(02)00809-6.
22. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438(7068):685–9. doi:10.1038/nature04303.
23. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452(7189):896–9. doi:10.1038/nature06783.
24. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87–98. doi:10.1016/j.cmet.2006.01.005.
25. Jopling CL, Schutz S, Sarnow P. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe. 2008;4(1):77–85. doi:10.1016/j.chom.2008.05.013.
26. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005;309(5740):1577–81. doi:10.1126/science.1113329.
27. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013;368(18):1685–94. doi:10.1056/NEJMoa1209026. The phase 2a results of miravirsen, an inhibitor against miR-122, in patients with hepatitis C virus. These are the most advanced clinical studies with anti-microRNA therapies and will pave the way for future miRNA-based therapeutics.
28. Soh J, Iqbal J, Queiroz J, Fernandez-Hernando C, Hussain MM, Soh J, et al. MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat Med. 2013;19(7):892–900. doi:10.1038/nm.3200. An elegant example of how miR-30c controls LDL cholesterol levels by targeting MTP, yet concomitantly reduces lipid synthesis by targeting LPGAT1, revitalizing hope for miR-30c as an MTP-targeting therapy for hypercholesterolemia.
29. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13(5):613–18. doi:10.1038/nm1582.
30. Matkovich SJ, Wang W, Tu Y, Eschenbacher WH, Dorn LE, Condorelli G, et al. MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res. 2010;106(1):166–75. doi:10.1161/CIRCRESAHA.109.202176.
31. Liu N, Bezprozvannaya S, Williams AH, Qi X, Richardson JA, Bassel-Duby R, et al. microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 2008;22(23):3242–54. doi:10.1101/gad.1738708.
32. Dong S, Ma W, Hao B, Hu F, Yan L, Yan X, et al. microRNA-21 promotes cardiac fibrosis and development of heart failure with preserved left ventricular ejection fraction by up-regulating Bcl-2. Int J Clin Exp Pathol. 2014;7(2):565–74.
33. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980–4. doi:10.1038/nature07511.
34. Kumarswamy R, Volkmann I, Jazbutyte V, Dangwal S, Park D-H, Thum T. Transforming growth factor-β-induced endothelial-to-mesenchymal transition is partly mediated by microRNA-21. Arterioscler, Thromb, Vasc Biol. 2012;32(2):361–9. doi:10.1161/ATVBAHA.111.234286.
35. Patrick DM, Montgomery RL, Qi X, Obad S, Kauppinen S, Hill JA, et al. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest. 2010;120(11):3912–16. doi:10.1172/JCI43604.
36. Montgomery RL, Hullinger TG, Semus HM, Dickinson BA, Seto AG, Lynch JM, et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation. 2011;124(14):1537–47. doi:10.1161/CIRCULATIONAHA.111.030932.
37. Callis TE, Pandya K, Seok HY, Tang R-h, Tatsuguchi M, Huang Z-p, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Investig. 2009;119(9):2772–86. doi:10.1172/JCI36154.2772.
38. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 2007;316(5824):575–9. doi:10.1126/science.1139089.
39. Grueter CE, van Rooij E, Johnson BA, DeLeon SM, Sutherland LB, Qi X, et al. A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell. 2012;149(3):671–83. doi:10.1016/j.cell.2012.03.029. An example of how a tissue-specific miRNA can regulate whole-body energy metabolism by targeting genes in the heart.
40. da Costa Martins PA, Salic K, Gladka MM, Armand AS, Leptidis S, el Azzouzi H, et al. MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol. 2010;12(12):1220–7. doi:10.1038/ncb2126.
41. Bang C, Fiedler J, Thum T. Cardiovascular importance of the microRNA-23/27/24 family. Microcirculation (New York, NY: 1994). 2012;19(3):208–14. doi:10.1111/j.1549-8719.2011.00153.
42. Zhou Q, Gallagher R, Ufret-Vincenty R, Li X, Olson EN, Wang S. Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23-27-24 clusters. Proc Natl Acad Sci U S A. 2011;108(20):8287–92. doi:10.1073/pnas.1105254108.
43. Fiedler J, Jazbutyte V, Kirchmaier BC, Gupta SK, Lorenzen J, Hartmann D, et al. MicroRNA-24 regulates vascularity after myocardial infarction. Circulation. 2011;124(6):720–30. doi:10.1161/CIRCULATIONAHA.111.039008.
44. Qian L, Van Laake LW, Huang Y, Liu S, Wendland MF, Srivastava D. miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes. J Exp Med. 2011;208(3):549–60. doi:10.1084/jem.20101547.
45. Wang S, Olson EN. AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev. 2009;19(3):205–11. doi:10.1016/j.gde.2009.04.002.
46. Wu W, Xiao H, Laguna-Fernandez A, Villarreal Jr G, Wang KC, Geary GG, et al. Flow-dependent regulation of Kruppel-like factor 2 is mediated by microRNA-92a. Circulation. 2011;124(5):633–41. doi:10.1161/CIRCULATIONAHA.110.005108.
47. Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science. 2009;324(5935):1710–13. doi:10.1126/science.1174381.
48. Loyer X, Potteaux S, Vion A-C, Guérin CL, Boulkroun S, Rautou P-E, et al. Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res. 2014;114(3):434–43. doi:10.1161/CIRCRESAHA.114.302213.
49. Hinkel R, Penzkofer D, Zühlke S, Fischer A, Husada W, Xu Q-F, et al. Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation. 2013;128(10):1066–75. doi:10.1161/CIRCULATIONAHA.113.001904.
50. Zhu H, Fan G-C. Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. Cardiovasc Res. 2012;94(2):284–92. doi:10.1093/cvr/cvr291.
51. Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15(2):272. doi:10.1016/j.devcel.2008.07.008.
52. Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15(2):261–71. doi:10.1016/j.devcel.2008.07.002.
53. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516–21. doi:10.1073/pnas.0707493105.
54. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2(100):ra81. doi:10.1126/scisignal.2000610.
55. Schober A, Nazari-Jahantigh M, Wei Y, Bidzhekov K, Gremse F, Grommes J, et al. MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1. Nat Med. 2014;20(4):368–76. doi:10.1038/nm.3487. This work is the first to describe how different “arms” of a mature microRNA, -3p versus -5p, can have divergent functions in regulating endothelial function in atherosclerosis.
56. Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, et al. MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 2009;23(18):2166–78. doi:10.1101/gad.1842409.
57. Cheng Y, Liu X, Yang J, Lin Y, Xu D-Z, Lu Q, et al. MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res. 2009;105(2):158–66. doi:10.1161/CIRCRESAHA.109.197517.
58. Boettger T, Beetz N, Kostin S, Schneider J, Kruger M, Hein L, et al. Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest. 2009;119(9):2634–47. doi:10.1172/JCI38864.
59. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, et al. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation. 2012;126(11 Suppl 1):S81–90. doi:10.1161/CIRCULATIONAHA.111.084186.
60. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007;104(5):1604–9. doi:10.1073/pnas.0610731104.
61. Graff JW, Dickson AM, Clay G, McCaffrey AP, Wilson ME. Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem. 2012;287(26):21816–25. doi:10.1074/jbc.M111.327031.
62. Nazari-Jahantigh M, Wei Y, Noels H, Akhtar S, Zhou Z, Koenen RR, et al. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J Clin Invest. 2012;122(11):4190–202. doi:10.1172/JCI61716.
63. Du F, Yu F, Wang Y, Hui Y, Carnevale K, Fu M, et al. MicroRNA-155 deficiency results in decreased macrophage inflammation and attenuated atherogenesis in apolipoprotein E-deficient mice. Arterioscler, Thromb, Vasc Biol. 2014;34(4):759–67. doi:10.1161/ATVBAHA.113.302701.
64. Donners MM, Wolfs IM, Stoger LJ, van der Vorst EP, Pottgens CC, Heymans S, et al. Hematopoietic miR155 deficiency enhances atherosclerosis and decreases plaque stability in hyperlipidemic mice. PLoS One. 2012;7(4):e35877. doi:10.1371/journal.pone.0035877.
65. Wei Y, Nazari-Jahantigh M, Chan L, Zhu M, Heyll K, Corbalan-Campos J, et al. The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation. 2013. doi:10.1161/CIRCULATIONAHA.112.000736.
66. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103(33):12481–6. doi:10.1073/pnas.0605298103.
67. Chassin C, Kocur M, Pott J, Duerr CU, Gütle D, Lotz M, et al. miR-146a mediates protective innate immune tolerance in the neonate intestine. Cell Host Microbe. 2010;8(4):358–68. doi:10.1016/j.chom.2010.09.005.
68. Perry MM, Sa M, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay M. Rapid changes in microRNA-146a expression negatively regulate the IL-1-induced inflammatory response in human lung alveolar epithelial cells. J Immunol. 2008;180(8):5689–98. doi:10.4049/jimmunol.180.8.5689.
69. Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208(6):1189–201. doi:10.1084/jem.20101823.
70. Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D, et al. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med. 2013;5(7):949–66. doi:10.1002/emmm.201202318.
71. Wei Y, Nazari-Jahantigh M, Neth P, Weber C, Schober A. MicroRNA-126, -145, and -155: a therapeutic triad in atherosclerosis? Arterioscler, Thromb, Vasc Biol. 2013;33(3):449–54. doi:10.1161/ATVBAHA.112.300279.
72. Chen X, Liang H, Zhang J, Zen K, Zhang C-Y. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol. 2012;22(3):125–32. doi:10.1016/j.tcb.2011.12.001.
73. Rayner KJ, Hennessy EJ. Extracellular communication via microRNA: lipid particles have a new message. J Lipid Res. 2013;54(5):1174–81. doi:10.1194/jlr.R034991.
74. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nature cell biology. 2011;13(4):423–33. doi:10.1038/ncb2210.
75. Ra B, Vickers KC. Intercellular transport of microRNAs. Arterioscler, Thromb, Vasc Biol. 2013;33(2):186–92. doi:10.1161/ATVBAHA.112.300139.
76. Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–56. doi:10.1038/ncb2441. One of the first examples of how extracellular miRNAs facilitate communication between neighboring cells during the progression of cardiovascular disease.
77. Halkein J, Tabruyn SP, Ricke-hoch M, Haghikia A, Nguyen N-q-n, Scherr M, et al. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest. 2013;123(5):2143–54. doi:10.1172/JCI64365.
78. Zhang Y, Liu D, Chen X, Li J, Li L, Bian Z, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol Cell. 2010;39(1):133–44. doi:10.1016/j.molcel.2010.06.010.
79. Chen L, Wang Y, Pan Y, Zhang L, Shen C, Qin G, et al. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem Biophys Res Commun. 2013;431(3):566–71. doi:10.1016/j.bbrc.2013.01.015.
80. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4):341–5. doi:10.1038/nbt.1807.
81. Development of new therapeutic drugs and biologics for rare diseases. In: Field MJ, Boat TJ, editors. Rare diseases and orphan products: accelerating research and development. Development of New Therapeutic Drugs and Biologics for Rare Diseases. Washington, D.C.: THE NATIONAL ACADEMIES PRESS (2010).
82. Brown WV, Rader DJ, Goldberg AC. JCL roundtable: drug treatment of severe forms of familial hypercholesterolemia. J Clin Lipidol. 2014;8(1):10–7. doi:10.1016/j.jacl.2013.09.004.
83. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010;107(5):677–84. doi:10.1161/CIRCRESAHA.109.215566.
84. Hoekstra M, van der Lans CA, Halvorsen B, Gullestad L, Kuiper J, Aukrust P, et al. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochem Biophys Res Commun. 2010;394(3):792–7. doi:10.1016/j.bbrc.2010.03.075.
85. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010;31(6):659–66. doi:10.1093/eurheartj/ehq013.
86. Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, et al. Plasma microRNA-499 as a biomarker of acute myocardial infarction. Clin Chem. 2010;56(7):1183–5. doi:10.1373/clinchem.2010.144121.
87. D’Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010;31(22):2765–73. doi:10.1093/eurheartj/ehq167.
88. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, et al. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010;3(6):499–506. doi:10.1161/CIRCGENETICS.110.957415.
89. Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, et al. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond). 2010;119(2):87–95. doi:10.1042/CS20090645.
90. Long G, Wang F, Duan Q, Yang S, Chen F, Gong W, et al. Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PloS One. 2012;7(12):e50926. doi:10.1371/journal.pone.0050926.
91. Voellenkle C, van Rooij J, Cappuzzello C, Greco S, Arcelli D, Di Vito L, et al. MicroRNA signatures in peripheral blood mononuclear cells of chronic heart failure patients. Physiol Genomics. 2010;42(3):420–6. doi:10.1152/physiolgenomics.00211.2009.
92. Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J. 2011;75(2):336–340. doi:10.1253/circj.CJ-10-0457.
93. Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106(6):1035–9. doi:10.1161/CIRCRESAHA.110.218297.
94. Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14(2):147–54. doi:10.1093/eurjhf/hfr155.
95. Fan KL, Zhang HF, Shen J, Zhang Q, Li XL. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J. 2013;65(1), 12–6. doi:10.1016/j.ihj.2012.12.022.