Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases

Journal of Biomedical Science - Tập 27 - Trang 1-16 - 2020
Chih-Fan Yeh1,2, Yu-Chen Eugene Chang1, Cheng-Yuan Lu1, Chin-Feng Hsuan3,4, Wei-Tien Chang5, Kai-Chien Yang1,2
1Graduate Institute and Department of Pharmacology, National Taiwan University School of Medicine, Taipei, Taiwan
2Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
3Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, Kaohsiung, Taiwan
4Department of Medicine, I-Shou University School of Medicine, Kaohsiung, Taiwan
5Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan

Tóm tắt

With the advances in deep sequencing-based transcriptome profiling technology, it is now known that human genome is transcribed more pervasively than previously thought. Up to 90% of the human DNA is transcribed, and a large proportion of the human genome is transcribed as long noncoding RNAs (lncRNAs), a heterogenous group of non-coding transcripts longer than 200 nucleotides. Emerging evidence suggests that lncRNAs are functional and contribute to the complex regulatory networks involved in cardiovascular development and diseases. In this article, we will review recent evidence on the roles of lncRNAs in the biological processes of cardiovascular development and disorders. The potential applications of lncRNAs as biomarkers and targets for therapeutics are also discussed.

Tài liệu tham khảo

Hannenhalli S, et al. Transcriptional genomics associates FOX transcription factors with human heart failure. Circulation. 2006;114(12):1269–76. Kittleson MM, et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation. 2004;110(22):3444–51. Margulies KB, et al. Mixed messages: transcription patterns in failing and recovering human myocardium. Circ Res. 2005;96(5):592–9. Matkovich SJ, et al. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation. 2009;119(9):1263–71. Ramani R, et al. A micro-ribonucleic acid signature associated with recovery from assist device support in 2 groups of patients with severe heart failure. J Am Coll Cardiol. 2011;58(22):2270–8. Mattick JS. The central role of RNA in human development and cognition. FEBS Lett. 2011;585(11):1600–16. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861–74. Navarro P, et al. Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program. Genes Dev. 2006;20(20):2787–92. Gupta RA, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6. Huarte M, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19. Guttman M, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477(7364):295–300. Hung T, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011;43(7):621–9. Faghihi MA, et al. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14(7):723–30. Johnson R. Long non-coding RNAs in Huntington's disease neurodegeneration. Neurobiol Dis. 2012;46(2):245–54. Calin GA, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer cell. 2007;12(3):215–29. Yildirim E, et al. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013;152(4):727–42. Garding A, et al. Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS Genet. 2013;9(4):e1003373. Zhao J, et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6. Beltran M, et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008;22(6):756–69. Ogawa Y, Sun BK, Lee JT. Intersection of the RNA interference and X-inactivation pathways. Science. 2008;320(5881):1336–41. Carrieri C, et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature. 2012;491(7424):454–7. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14. Yang KC, et al. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support. Circulation. 2014;129(9):1009–21. Li H, et al. Identification of cardiac long non-coding RNA profile in human dilated cardiomyopathy. Cardiovasc Res. 2018;114(5):747–58. Saddic LA, et al. The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle. Circ Cardiovasc Genet. 2017;10:1. Ounzain S, et al. Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs. Eur Heart J. 2015;36(6):353–68a. Zangrando J, et al. Identification of candidate long non-coding RNAs in response to myocardial infarction. BMC Genomics. 2014;15:460. Viereck J, et al. Long noncoding RNA Chast promotes cardiac remodeling. Sci Transl Med. 2016;8(326):326ra22. Wang Z, et al. The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nat Med. 2016;22(10):1131–9. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol. 2018;15(7):387–407. Han P, et al. A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014;514(7520):102–6. Luo Y, et al. The mechanism of myocardial hypertrophy regulated by the interaction between mhrt and myocardin. Cell Signal. 2018;43:11–20. Wang K, et al. The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489. Circ Res. 2014;114(9):1377–88. Wo Y, et al. Long non-coding RNA CHRF facilitates cardiac hypertrophy through regulating Akt3 via miR-93. Cardiovasc Pathol. 2018;35:29–36. Zhu XH, et al. LncRNA MIAT enhances cardiac hypertrophy partly through sponging miR-150. Eur Rev Med Pharmacol Sci. 2016;20(17):3653–60. Li Z, et al. Long noncoding RNA myocardial infarctionassociated transcript is associated with the microRNA1505p/P300 pathway in cardiac hypertrophy. Int J Mol Med. 2018;42(3):1265–72. Li Y, et al. LncRNA myocardial infarction-associated transcript (MIAT) contributed to cardiac hypertrophy by regulating TLR4 via miR-93. Eur J Pharmacol. 2018;818:508–17. Liu, L., et al., The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy. Cardiovasc Res, 2016. 111(1): p. 56–65. Lai Y, et al. HOTAIR functions as a competing endogenous RNA to regulate PTEN expression by inhibiting miR-19 in cardiac hypertrophy. Mol Cell Biochem. 2017;432(1–2):179–87. Jiang F, Zhou X, Huang J. Long non-coding RNA-ROR mediates the reprogramming in cardiac hypertrophy. PLoS One. 2016;11(4):e0152767. Zhang Q, et al. Long noncoding RNA MAGI1-IT1 regulates cardiac hypertrophy by modulating miR-302e/DKK1/Wnt/beta-catenin signaling pathway. J Cell Physiol. 2019. Wu H, et al. Long noncoding RNA Meg3 regulates cardiomyocyte apoptosis in myocardial infarction. Gene Ther. 2018;25(8):511–23. Lv L, et al. The lncRNA Plscr4 controls cardiac hypertrophy by regulating miR-214. Mol Ther Nucleic Acids. 2018;10:387–97. Wang Y, et al. SP1-SYNE1-AS1-miR-525-5p feedback loop regulates Ang-II-induced cardiac hypertrophy. J Cell Physiol. 2019;234(8):14319–29. Chen Y, et al. The long noncoding RNA XIST protects cardiomyocyte hypertrophy by targeting miR-330-3p. Biochem Biophys Res Commun. 2018;505(3):807–15. Xiao L, et al. The long noncoding RNA XIST regulates cardiac hypertrophy by targeting miR-101. J Cell Physiol. 2019;234(8):13680–92. Qu X, et al. MIAT is a pro-fibrotic Long non-coding RNA governing cardiac fibrosis in post-infarct myocardium. Sci Rep. 2017;7:42657. Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis. Circ Res. 2016;119(1):91–112. Liu CY, et al. LncRNA CAIF inhibits autophagy and attenuates myocardial infarction by blocking p53-mediated myocardin transcription. Nat Commun. 2018;9(1):29. Greco S, et al. Increased BACE1-AS long noncoding RNA and beta-amyloid levels in heart failure. Cardiovasc Res. 2017;113(5):453–63. Wang K, et al. CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation. Nat Commun. 2014;5:3596. Wang K, et al. APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nat Commun. 2015;6:6779. Wang K, et al. The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873. Cell Death Differ. 2016;23(8):1394–405. Micheletti R, et al. The long noncoding RNA Wisper controls cardiac fibrosis and remodeling. Sci Transl Med. 2017;9:395. Piccoli MT, et al. Inhibition of the cardiac fibroblast-enriched lncRNA Meg3 prevents cardiac fibrosis and diastolic dysfunction. Circ Res. 2017;121(5):575–83. Huang S, et al. Long noncoding RNA MALAT1 mediates cardiac fibrosis in experimental postinfarct myocardium mice model. J Cell Physiol. 2019;234(3):2997–3006. Lu Y, et al. MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation. 2010;122(23):2378–87. Li Z, et al. Altered long non-coding RNA expression profile in rabbit atria with atrial fibrillation: TCONS_00075467 modulates atrial electrical remodeling by sponging miR-328 to regulate CACNA1C. J Mol Cell Cardiol. 2017;108:73–85. Zhao ZH, et al. Long non-coding RNA MALAT1 functions as a mediator in cardioprotective effects of fentanyl in myocardial ischemia-reperfusion injury. Cell Biol Int. 2017;41(1):62–70. Liu W, et al. High-mobility group box 1 (HMGB1) downregulates cardiac transient outward potassium current (Ito) through downregulation of Kv4.2 and Kv4.3 channel transcripts and proteins. J Mol Cell Cardiol. 2010;49(3):438–48. Zhu P, et al. Long noncoding RNA MALAT1 downregulates cardiac transient outward potassium current by regulating miR-200c/HMGB1 pathway. J Cell Biochem. 2018;119(12):10239–49. Long QQ, et al. Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure. J Am Heart Assoc. 2017;6:12. Zhang Y, et al. Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling. Nat Commun. 2018;9(1):4176. Zhang Y, et al. LncRNA ZFAS1 as a SERCA2a inhibitor to cause intracellular Ca(2+) overload and contractile dysfunction in a mouse model of myocardial infarction. Circ Res. 2018;122(10):1354–68. Chilley PM, et al. The POLARIS peptide of Arabidopsis regulates auxin transport and root growth via effects on ethylene signaling. Plant Cell. 2006;18(11):3058–72. Bi P, et al. Control of muscle formation by the fusogenic micropeptide myomixer. Science. 2017;356(6335):323–7. Stein CS, et al. Mitoregulin: a lncRNA-encoded microprotein that supports mitochondrial Supercomplexes and respiratory efficiency. Cell Rep. 2018;23(13):3710–20 e8. Magny EG, et al. Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science. 2013;341(6150):1116–20. Nelson BR, et al. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science. 2016;351(6270):271–5. Anderson DM, et al. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance. Cell. 2015;160(4):595–606. Lusis AJ. Atherosclerosis. Nature. 2000;407(6801):233–41. Braunwald E. Shattuck lecture--cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med. 1997;337(19):1360–9. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340(2):115–26. Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–74. Singh KK, et al. Endothelial long non-coding RNAs regulated by oxidized LDL. Mol Cell Biochem. 2017;431(1–2):139–49. Singh KK, et al. A global profile of glucose-sensitive endothelial-expressed long non-coding RNAs. Can J Physiol Pharmacol. 2016;94(9):1007–14. Lustig O, et al. Expression of the imprinted gene H19 in the human fetus. Mol Reprod Dev. 1994;38(3):239–46. Kim DK, et al. H19, a developmentally regulated gene, is reexpressed in rat vascular smooth muscle cells after injury. J Clin Invest. 1994;93(1):355–60. Tao SC, et al. Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds. Drug Deliv. 2018;25(1):241–55. Michalik KM, et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res. 2014;114(9):1389–97. Liu JY, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus. Cell Death Dis. 2014;5:e1506. Zhang X, et al. Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia. Int J Mol Sci. 2018;19:6. Liu J, et al. Downregulation of the Long non-coding RNA Meg3 promotes angiogenesis after ischemic brain injury by activating notch signaling. Mol Neurobiol. 2017;54(10):8179–90. Boon RA, et al. Long noncoding RNA Meg3 controls endothelial cell aging and function: implications for regenerative angiogenesis. J Am Coll Cardiol. 2016;68(23):2589–91. Gordon FE, et al. Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology. 2010;151(6):2443–52. Qiu GZ, et al. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. Biochem Biophys Res Commun. 2016;471(1):135–41. Hu YW, et al. Long noncoding RNA NEXN-AS1 mitigates atherosclerosis by regulating the actin-binding protein NEXN. J Clin Invest. 2019;129(3):1115–28. Leisegang MS, et al. Long noncoding RNA MANTIS facilitates endothelial Angiogenic function. Circulation. 2017;136(1):65–79. Leisegang MS, et al. Pleiotropic effects of laminar flow and statins depend on the Kruppel-like factor-induced lncRNA MANTIS. Eur Heart J. 2019;40(30):2523–33. Samani NJ, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007;357(5):443–53. Helgadottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316(5830):1491–3. McPherson R, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316(5830):1488–91. Myocardial Infarction Genetics, C, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41(3):334–41. Holdt LM, et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet. 2013;9(7):e1003588. Tan P, et al. LncRNA-ANRIL inhibits cell senescence of vascular smooth muscle cells by regulating miR-181a/Sirt1. Biochem Cell Biol. 2019. Lo Sardo V, et al. Unveiling the role of the Most impactful cardiovascular risk locus through haplotype editing. Cell. 2018;175(7):1796–810 e20. Li DY, et al. H19 induces abdominal aortic aneurysm development and progression. Circulation. 2018;138(15):1551–68. Zhang L, et al. H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b/WNT/beta-catenin in ox-LDL -stimulated vascular smooth muscle cells. J Biomed Sci. 2018;25(1):11. Hou J, et al. Long noncoding RNA H19 upregulates vascular endothelial growth factor a to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p. Stem Cell Res Ther. 2018;9(1):109. Lino Cardenas CL, et al. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nat Commun. 2018;9(1):1009. Li P, et al. A liver-enriched long non-coding RNA, lncLSTR, regulates systemic lipid metabolism in mice. Cell Metab. 2015;21(3):455–67. Sallam T, et al. Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis. Nature. 2016;534(7605):124–8. Tontonoz P, et al. Long noncoding RNA facilitated gene therapy reduces atherosclerosis in a murine model of familial hypercholesterolemia. Circulation. 2017;136(8):776–8. Sallam T, et al. Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA. Nat Med. 2018;24(3):304–12. Klattenhoff CA, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell. 2013;152(3):570–83. Guo X, et al. A Linc1405/Eomes complex promotes cardiac mesoderm specification and Cardiogenesis. Cell Stem Cell. 2018;22(6):893–908 e6. Ounzain S, et al. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. J Mol Cell Cardiol. 2015;89(Pt A):98–112. Grote P, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell. 2013;24(2):206–14. Banerjee P, et al. Long noncoding RNA RP11-380D23.2 drives distal-proximal patterning of the lung by regulating PITX2 expression. Stem Cells. 2018;36(2):218–29. Gore-Panter SR, et al. PANCR, the PITX2 adjacent noncoding RNA, is expressed in human left atria and regulates PITX2c expression. Circ Arrhythm Electrophysiol. 2016;9(1):e003197. Welsh IC, et al. Chromatin architecture of the Pitx2 locus requires CTCF- and Pitx2-dependent asymmetry that mirrors embryonic gut laterality. Cell Rep. 2015;13(2):337–49. Anderson KM, et al. Transcription of the non-coding RNA upperhand controls Hand2 expression and heart development. Nature. 2016;539(7629):433–6. Han X, et al. The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2. Development. 2019;146:13. Ritter N, et al. The lncRNA locus Handsdown regulates cardiac gene programs and is essential for early mouse development. Dev Cell. 2019. Wang Q, et al. Potential association of long noncoding RNA HA117 with tetralogy of Fallot. Genes Dis. 2018;5(2):185–90. Garg N, et al. microRNA-17-92 cluster is a direct Nanog target and controls neural stem cell through Trp53inp1. EMBO J. 2013;32(21):2819–32. Deleersnijder W, et al. Isolation of markers for chondro-osteogenic differentiation using cDNA library subtraction. Molecular cloning and characterization of a gene belonging to a novel multigene family of integral membrane proteins. J Biol Chem. 1996;271(32):19475–82. Cai B, et al. The Long noncoding RNA CAREL controls cardiac regeneration. J Am Coll Cardiol. 2018;72(5):534–50. Ponnusamy M, et al. Long noncoding RNA CPR (Cardiomyocyte proliferation regulator) regulates Cardiomyocyte proliferation and cardiac repair. Circulation. 2019;139(23):2668–84. Thommes P, et al. Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein. Nucleic Acids Res. 1992;20(5):1069–74. Wang J, et al. A long noncoding RNA NR_045363 controls cardiomyocyte proliferation and cardiac repair. J Mol Cell Cardiol. 2019;127:105–14. Chen G, et al. Loss of long non-coding RNA CRRL promotes cardiomyocyte regeneration and improves cardiac repair by functioning as a competing endogenous RNA. J Mol Cell Cardiol. 2018;122:152–64. Chen Y, et al. Long non-coding RNA ECRAR triggers post-natal myocardial regeneration by activating ERK1/2 signaling. Mol Ther. 2019;27(1):29–45. Kajstura J, et al. The IGF-1-IGF-1 receptor system modulates myocyte proliferation but not myocyte cellular hypertrophy in vitro. Exp Cell Res. 1994;215(2):273–83. Huang Y, et al. Igf signaling is required for Cardiomyocyte proliferation during Zebrafish heart development and regeneration. PLoS One. 2013;8(6):e67266. Li B, et al. Sirt1 antisense Long noncoding RNA promotes Cardiomyocyte proliferation by enhancing the stability of Sirt1. J Am Heart Assoc. 2018;7(21):e009700. Li X, et al. Loss of AZIN2 splice variant facilitates endogenous cardiac regeneration. Cardiovasc Res. 2018;114(12):1642–55. Congrains A, et al. Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B. Atherosclerosis. 2012;220(2):449–55. Holdt LM, et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol. 2010;30(3):620–7. Vausort M, Wagner DR, Devaux Y. Long noncoding RNAs in patients with acute myocardial infarction. Circ Res. 2014;115(7):668–77. Yang Y, et al. Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease. Clin Sci (Lond). 2015;129(8):675–85. Cai Y, et al. Circulating ‘lncRNA OTTHUMT00000387022’ from monocytes as a novel biomarker for coronary artery disease. Cardiovasc Res. 2016;112(3):714–24. Zhang Z, et al. Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population. Sci Rep. 2017;7(1):7491. Kumarswamy R, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res. 2014;114(10):1569–75. Chen L, et al. Global transcriptomic study of atherosclerosis development in rats. Gene. 2016;592(1):43–8. Yin Q, Wu A, Liu M. Plasma Long non-coding RNA (lncRNA) GAS5 is a new biomarker for coronary artery disease. Med Sci Monit. 2017;23:6042–8. Chen L, et al. Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis. PLoS One. 2017;12(9):e0185406. Bell RD, et al. Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA. Arterioscler Thromb Vasc Biol. 2014;34(6):1249–59. Boulberdaa M, et al. A role for the Long noncoding RNA SENCR in commitment and function of endothelial cells. Mol Ther. 2016;24(5):978–90. Ziaee S, et al. Non-invasive diagnosis of early-onset coronary artery disease based on cell type-specific gene expression analyses. Biomed Pharmacother. 2018;108:1115–22. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(5 Suppl 3):S112–9. Go AS, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305. Lai CF, et al. Circulating long noncoding RNA DKFZP434I0714 predicts adverse cardiovascular outcomes in patients with end-stage renal disease. Int J Cardiol. 2019;277:212–9.