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The Function and Therapeutic Potential of Circular RNA in Cardiovascular Diseases

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Abstract

Circular RNA (circRNA) has a closed-loop structure, and its 3’ and 5’ ends are directly covalently connected by reverse splicing, which is more stable than linear RNA. CircRNAs usually possess microRNA (miRNA) binding sites, which can bind miRNAs and inhibit miRNA function. Many studies have shown that circRNAs are involved in the processes of cell senescence, proliferation and apoptosis and a series of signalling pathways, playing an important role in the prevention and treatment of diseases. CircRNAs are potential biological diagnostic markers and therapeutic targets for cardiovascular diseases (CVDs). To identify biomarkers and potential effective therapeutic targets without toxicity for heart disease, we summarize the biogenesis, biology, characterization and functions of circRNAs in CVDs, hoping that this information will shed new light on the prevention and treatment of CVDs.

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Abbreviations

circRNA:

Circular RNA

miRNA:

MicroRNA

CVD:

Cardiovascular disease

ncRNA:

Noncoding RNA

RBP:

RNA binding protein

RNAPol:

RNA polymerase

ecRNA:

Exon circRNA

ciRNA:

Intronic circRNA

elciRNA:

Exon–intron circRNA

MRE:

MiRNA response element

m6A:

N6-methyladenosine

PKR:

Double-stranded RNA-dependent protein kinase

VSMC:

Vascular smooth muscle cell

EMT:

Epithelial-mesenchymal transition

PES 1:

Pescadillo homologue 1

RCA:

Rolling circle amplification

IRES:

Internal ribosome entry site

MFACR:

Mitochondrial fission and apoptosis-related circRNA

EIF4A3:

Eukaryotic translation initiation factor 4A3

MICRA:

Myocardial infarction-related circRNA

I/R:

Ischaemia/reperfusion

RISK:

Reperfusion injury saving kinase

HRCR:

Heart-related circRNA

SRF:

Serum responsive factor

CTGF:

Connective tissue growth factor

Adrb1:

Adrenergic receptor β1

ADCY6:

Adenylate cyclase 6

TGF:

Transforming growth factor

AF:

Atrial fibrillation

EH:

Essential hypertension

SH:

Secondary hypertension

AAA:

Abdominal aortic aneurysm

BNP:

B-type natriuretic peptide

ANP:

Atrial natriuretic peptide

CRP:

C-reactive protein

IL-6:

Interleukin-6

qPCR:

Quantitative polymerase chain reaction

FISH:

Fluorescence in situ hybridization

References

  1. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular rnas are a large class of animal rnas with regulatory potency. Nature. 2013;495(7441):333–8.

    Article  CAS  Google Scholar 

  2. Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. Viroids are single-stranded covalently closed circular rna molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976;73(11):3852–6.

    Article  CAS  Google Scholar 

  3. Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of rna in the cytoplasm of eukaryotic cells. Nature. 1979;280(5720):339–40.

    Article  CAS  Google Scholar 

  4. Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, et al. Circular transcripts of the testis-determining gene sry in adult mouse testis. Cell. 1993;73(5):1019–30.

    Article  CAS  Google Scholar 

  5. Cocquerelle C, Mascrez B, Hétuin D, Bailleul B. Mis-splicing yields circular rna molecules. FASEB J. 1993;7(1):155–60.

    Article  CAS  Google Scholar 

  6. Chen X, Han P, Zhou T, Guo X, Song X, Li Y. Circrnadb: a comprehensive database for human circular rnas with protein-coding annotations. Sci Rep. 2016;6:34985.

    Article  CAS  Google Scholar 

  7. Abdelmohsen K, Panda A, Munk R, Grammatikakis I, Dudekula D, De S, et al. Identification of hur target circular rnas uncovers suppression of pabpn1 translation by circpabpn1. RNA Biol. 2017;14(3):361–9.

    Article  Google Scholar 

  8. Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. Circrna biogenesis competes with pre-mrna splicing. Mol Cell. 2014;56(1):55–66.

    Article  CAS  Google Scholar 

  9. Ying C, Guohai Y, Ye Z, et al. High glucose-induced circhipk3 downregulation mediates endothelial cell injury. Biochem Biophys Res Commun. 2018;507(1–4):362–8.

    Google Scholar 

  10. Lu D, Thum T. Rna-based diagnostic and therapeutic strategies for cardiovascular disease. Nat Rev Cardiol. 2019;16(11):661–74.

    Article  Google Scholar 

  11. Zhang TR, Huang WQ. Angiogenic circular rnas: a new landscape in cardiovascular diseases. Microvasc Res. 2020;129:103983.

    Article  CAS  Google Scholar 

  12. Chen I, Chen CY, Chuang TJ. Biogenesis, identification, and function of exonic circular rnas. Wiley Interdiscip Rev RNA. 2015;6(5):563–79.

    Article  CAS  Google Scholar 

  13. Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, et al. Exon-intron circular rnas regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22(3):256–64.

    Article  Google Scholar 

  14. Kelly SGC, Cook PR, Papantonis A. Exon skipping is correlated with exon circularization. J Mol Biol. 2015;427(15):2414–7.

    Article  CAS  Google Scholar 

  15. Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, et al. Circular intronic long noncoding rnas. Mol Cell. 2013;51(6):792–806.

    Article  CAS  Google Scholar 

  16. Vo J, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, et al. The landscape of circular rna in cancer. Cell. 2019;176(4):869-81.e13.

    Article  CAS  Google Scholar 

  17. Suzuki H, Tsukahara T. A view of pre-mrna splicing from rnase r resistant rnas. Int J Mol Sci. 2014;15(6):9331–42.

    Article  CAS  Google Scholar 

  18. Du W, Yang W, Chen Y, Wu Z, Foster F, Yang Z, et al. Foxo3 circular rna promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J. 2017;38(18):1402–12.

    CAS  Google Scholar 

  19. Cai J, Chen Z, Wang J, Wang J, Chen X, Liang L, et al. Circhectd1 facilitates glutaminolysis to promote gastric cancer progression by targeting mir-1256 and activating β-catenin/c-myc signaling. Cell Death Dis. 2019;10(8):576.

    Article  Google Scholar 

  20. Qu S, Liu Z, Yang X, Zhou J, Yu H, Zhang R, et al. The emerging functions and roles of circular rnas in cancer. Cancer Lett. 2018;414:301–9.

    Article  CAS  Google Scholar 

  21. Wen G, Zhou T, Gu W. The potential of using blood circular rna as liquid biopsy biomarker for human diseases. Protein Cell. 2020.

  22. Huang A, Zheng H, Wu Z, Chen M, Huang Y. Circular rna-protein interactions: functions, mechanisms, and identification. Theranostics. 2020;10(8):3503–17.

    Article  CAS  Google Scholar 

  23. Hansen T, Wiklund E, Bramsen J, Villadsen S, Statham A, Clark S, et al. Mirna-dependent gene silencing involving ago2-mediated cleavage of a circular antisense rna. EMBO J. 2011;30(21):4414–22.

    Article  CAS  Google Scholar 

  24. Park O, Ha H, Lee Y, Boo S, Kwon D, Song H, et al. Endoribonucleolytic cleavage of ma-containing rnas by rnase p/mrp complex. Mol Cell. 2019;74(3):494-507.e8.

    Article  CAS  Google Scholar 

  25. Fischer J, Busa V, Shao Y, Leung A. Structure-mediated rna decay by upf1 and g3bp1. Mol Cell. 2020;78(1):70-84.e6.

    Article  CAS  Google Scholar 

  26. Jia R, Xiao M, Li Z, Shan G, Huang C. Defining an evolutionarily conserved role of gw182 in circular rna degradation. Cell Discov. 2019;5:45.

    Article  Google Scholar 

  27. Liu C, Li X, Nan F, Jiang S, Gao X, Guo S, et al. Structure and degradation of circular rnas regulate pkr activation in innate immunity. Cell. 2019;177(4):865-80.e21.

    Article  CAS  Google Scholar 

  28. Liang D, Tatomer DC, Luo Z, Wu H, Yang L, Chen L-L, et al. The output of protein-coding genes shifts to circular rnas when the pre-mrna processing machinery is limiting. Mol Cell. 2017;68(5):940-54.e3.

    Article  CAS  Google Scholar 

  29. Beermann J, Piccoli M, Viereck J, Thum T. Non-coding rnas in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev. 2016;96(4):1297–325.

    Article  CAS  Google Scholar 

  30. Ebert MS, Neilson JR, Sharp PA. Microrna sponges: competitive inhibitors of small rnas in mammalian cells. Nat Methods. 2007;4(9):721–6.

    Article  CAS  Google Scholar 

  31. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mrnas regulates tumour biology. Nature. 2010;465(7301):1033–8.

    Article  CAS  Google Scholar 

  32. Zhao F, Chen T, Jiang N. Cdr1as/mir-7/ckap4 axis contributes to the pathogenesis of abdominal aortic aneurysm by regulating the proliferation and apoptosis of primary vascular smooth muscle cells. Exp Ther Med. 2020;19(6):3760–6.

    CAS  Google Scholar 

  33. Piwecka M, Glazar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, et al. Loss of a mammalian circular rna locus causes mirna deregulation and affects brain function. Science. 2017;357(6357):eaam8526.

    Article  Google Scholar 

  34. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural rna circles function as efficient microrna sponges. Nature. 2013;495(7441):384–8.

    Article  CAS  Google Scholar 

  35. Quan H, Chen Q, Wang K, Wang Q, Lu M, Zhang Y, et al. Exendin-4 reversed the pc12 cell damage induced by circrna cdr1as/mir-671/gsk3β signaling pathway. J Mol Neurosci. 2020;71(4):778–89.

    Article  Google Scholar 

  36. Dang R, Liu F, Li Y. Circular rna hsa_circ_0010729 regulates vascular endothelial cell proliferation and apoptosis by targeting the mir-186/hif-1α axis. Biochem Biophys Res Commun. 2017;490(2):104–10.

    Article  CAS  Google Scholar 

  37. Zhuang J, Li T, Hu X, Ning M, Gao W, Lang Y, et al. Circ_chfr expedites cell growth, migration and inflammation in ox-ldl-treated human vascular smooth muscle cells via the mir-214-3p/wnt3/β-catenin pathway. Eur Rev Med Pharmacol Sci. 2020;24(6):3282–92.

    Google Scholar 

  38. Bressin A, Schulte-Sasse R, Figini D, Urdaneta EC, Beckmann BM, Marsico A. Tripepsvm: de novo prediction of rna-binding proteins based on short amino acid motifs. Nucleic Acids Res. 2019;47(9):4406–17.

    Article  CAS  Google Scholar 

  39. Zang J, Lu D, Xu A. The interaction of circrnas and rna binding proteins: an important part of circrna maintenance and function. J Neurosci Res. 2020;98(1):87–97.

    Article  CAS  Google Scholar 

  40. Ma S, Kong S, Wang F, Ju S. Circrnas: biogenesis, functions, and role in drug-resistant tumours. Mol Cancer. 2020;19(1):119.

    Article  CAS  Google Scholar 

  41. Zeng Y, Du W, Wu Y, Yang Z, Awan F, Li X, et al. A circular rna binds to and activates akt phosphorylation and nuclear localization reducing apoptosis and enhancing cardiac repair. Theranostics. 2017;7(16):3842–55.

    Article  CAS  Google Scholar 

  42. Conn S, Pillman K, Toubia J, Conn V, Salmanidis M, Phillips C, et al. The rna binding protein quaking regulates formation of circrnas. Cell. 2015;160(6):1125–34.

    Article  CAS  Google Scholar 

  43. Holdt L, Stahringer A, Sass K, Pichler G, Kulak N, Wilfert W, et al. Circular non-coding rna anril modulates ribosomal rna maturation and atherosclerosis in humans. Nat Commun. 2016;7:12429.

    Article  CAS  Google Scholar 

  44. Abe N, Matsumoto K, Nishihara M, Nakano Y, Shibata A, Maruyama H, et al. Rolling circle translation of circular rna in living human cells. Sci Rep. 2015;5:16435.

    Article  CAS  Google Scholar 

  45. Santer L, Bär C, Thum T. Circular rnas: a novel class of functional rna molecules with a therapeutic perspective. Mol Ther. 2019;27(8):1350–63.

    Article  CAS  Google Scholar 

  46. Lei M, Zheng G, Ning Q, Zheng J, Dong D. Translation and functional roles of circular rnas in human cancer. Mol Cancer. 2020;19(1):30.

    Article  CAS  Google Scholar 

  47. Pamudurti N, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, et al. Translation of circrnas. Mol Cell. 2017;66(1):9-21.e7.

    Article  CAS  Google Scholar 

  48. Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, et al. Circ-znf609 is a circular rna that can be translated and functions in myogenesis. Mol Cell. 2017;66(1):22-37.e9.

    Article  CAS  Google Scholar 

  49. van Heesch S, Witte F, Schneider-Lunitz V, Schulz J, Adami E, Faber A, et al. The translational landscape of the human heart. Cell. 2019;178(1):242-60.e29.

    Article  Google Scholar 

  50. Liu J, Liu T, Wang X, He A. Circles reshaping the rna world: from waste to treasure. Mol Cancer. 2017;16(1):58.

    Article  CAS  Google Scholar 

  51. McAloon C, Boylan L, Hamborg T, Stallard N, Osman F, Lim P, et al. The changing face of cardiovascular disease 2000–2012: an analysis of the world health organisation global health estimates data. Int J Cardiol. 2016;224:256–64.

    Article  Google Scholar 

  52. Members WG, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38.

    Google Scholar 

  53. Geng HH, Rui L, Su YM, Jie X, Min P, Cai XX, et al. The circular rna cdr1as promotes myocardial infarction by mediating the regulation of mir-7a on its target genes expression. Plos One. 2016;11(3):e0151753.

    Article  Google Scholar 

  54. Wang K, Gan T-Y, Li N, Liu C-Y, Zhou L-Y, Gao J-N, et al. Circular rna mediates cardiomyocyte death via mirna-dependent upregulation of mtp18 expression. Cell Death Differ. 2017;24(6):1111–20.

    Article  CAS  Google Scholar 

  55. Lidong Cai, Baozhen Qi, Xiaoyu Wu, et al. Circular rna ttc3 regulates cardiac function after myocardial infarction by sponging mir-15b. J Mol Cell Cardiol. 2019;130:10–22.

    Article  Google Scholar 

  56. Huang S, Li X, Zheng H, Si X, Li B, Wei G, et al. Loss of super-enhancer-regulated circrna nfix induces cardiac regeneration after myocardial infarction in adult mice. Circulation. 2019;139(25):2857–76.

    Article  CAS  Google Scholar 

  57. Li M, Ding W, Tariq MA, Chang W, Zhang X, Xu W, et al. A circular transcript of ncx1 gene mediates ischemic myocardial injury by targeting mir-133a-3p. Theranostics. 2018;8(21):5855–69.

    Article  CAS  Google Scholar 

  58. Zhou L-Y, Zhai M, Huang Y, Sheng Xu, An T, Wang Y-H, et al. The circular rna acr attenuates myocardial ischemia/reperfusion injury by suppressing autophagy via modulation of the pink1/fam65b pathway. Cell Death Differ. 2018;26(7):1299–315.

    Article  Google Scholar 

  59. Li Y, Ren S, Xia J, Wei Y, Xi Y. Eif4a3-induced circ-bnip3 aggravated hypoxia-induced injury of h9c2 cells by targeting mir-27a-3p/bnip3. Mol Ther Nucleic Acids. 2020;19:533–45.

    Article  CAS  Google Scholar 

  60. Salgado-Somoza A, Zhang L, Vausort M, Devaux Y. The circular rna micra for risk stratification after myocardial infarction. International journal of cardiology. Heart Vasc. 2017;17:33–6.

    Article  Google Scholar 

  61. Bai X, Niu R, Liu J, Pan X, Wang F, Yang W, et al. Roles of noncoding rnas in the initiation and progression of myocardial ischemia-reperfusion injury. Epigenomics. 2021;13(9):715–43.

    Article  CAS  Google Scholar 

  62. Song Y, Zhao L, Wang B, Sun J, Hu J, Zhu X, et al. The circular rna tlk1 exacerbates myocardial ischemia/reperfusion injury via targeting mir-214/ripk1 through tnf signaling pathway. Free Radical Biol Med. 2020;155:69–80.

    Article  CAS  Google Scholar 

  63. Chen L, Luo W, Zhang W, Chu H, Wang J, Dai X, et al. Circdlpag4/hectd1 mediates ischaemia/reperfusion injury in endothelial cells via er stress. RNA Biol. 2020;17(2):240–53.

    Article  CAS  Google Scholar 

  64. Xiao Y, Oumarou DB, Wang S, Liu Y. Circular rna involved in the protective effect of Malva sylvestris l. On myocardial ischemic/re-perfused injury. Front Pharmacol. 2020;11:520486.

    Article  CAS  Google Scholar 

  65. Altesha M, Ni T, Khan A, Liu K, Zheng X. Circular rna in cardiovascular disease. J Cell Physiol. 2019;234(5):5588–600.

    Article  CAS  Google Scholar 

  66. Zhang CL, Long TY, Bi SS, Sheikh SA, Li F. Circpan3 ameliorates myocardial ischaemia/reperfusion injury by targeting mir-421/pink1 axis-mediated autophagy suppression. Lab Invest. 2021;101(1):89–103.

    Article  CAS  Google Scholar 

  67. Wang K, Long B, Liu F, Wang J, Liu C, Zhao B, et al. A circular rna protects the heart from pathological hypertrophy and heart failure by targeting mir-223. Eur Heart J. 2016;37(33):2602–11.

    Article  CAS  Google Scholar 

  68. Lim T, Aliwarga E, Luu T, Li Y, Ng S, Annadoray L, et al. Targeting the highly abundant circular rna circslc8a1 in cardiomyocytes attenuates pressure overload induced hypertrophy. Cardiovasc Res. 2019;115(14):1998–2007.

    Article  CAS  Google Scholar 

  69. Zhang Y, Chen B. Silencing circ_0062389 alleviates cardiomyocyte apoptosis in heart failure rats via modulating tgf-β1/smad3 signaling pathway. Gene. 2021;766:145154.

    Article  CAS  Google Scholar 

  70. Han J, Zhang L, Hu L, Yu H, Xu F, Yang B, et al. Circular rna-expression profiling reveals a potential role of hsa_circ_0097435 in heart failure via sponging multiple micrornas. Front Genet. 2020;11:212.

    Article  CAS  Google Scholar 

  71. Deng Y, Wang J, Xie G, Zeng X, Li H. Circ-hipk3 strengthens the effects of adrenaline in heart failure by mir-17-3p - adcy6 axis. Int J Biol Sci. 2019;15(11):2484–96.

    Article  CAS  Google Scholar 

  72. Zaiou M. Circular rnas as potential biomarkers and therapeutic targets for metabolic diseases. Adv Exp Med Biol. 2019;1134:177–91.

    Article  CAS  Google Scholar 

  73. Zaiou M. Circular rnas in hypertension: challenges and clinical promise. Hypertens Res. 2019;42(11):1653–63.

    Article  Google Scholar 

  74. Zhang S, Chen X, Li C, Li X, Liu C, Liu B, et al. Identification and characterization of circular rnas as a new class of putative biomarkers in diabetes retinopathy. Invest Ophthalmol Vis Sci. 2017;58(14):6500–9.

    Article  CAS  Google Scholar 

  75. Zhou B, Yu J. A novel identified circular rna, circrna_010567, promotes myocardial fibrosis via suppressing mir-141 by targeting tgf-β1. Biochem Biophys Res Commun. 2017;487(4):769–75.

    Article  CAS  Google Scholar 

  76. Yang F, Li A, Qin Y, Che H, Wang Y, Lv J, et al. A novel circular rna mediates pyroptosis of diabetic cardiomyopathy by functioning as a competing endogenous rna. Mol Ther Nucleic Acids. 2019;17:636–43.

    Article  CAS  Google Scholar 

  77. Bazan HA, Hatfield SA, Brug A, Brooks AJ, Lightell DJ Jr, Woods TC. Carotid plaque rupture is accompanied by an increase in the ratio of serum circr-284 to mir-221 levels. Circ-Cardiovasc Genet. 2017;10(4):e001720.

    Article  CAS  Google Scholar 

  78. Ernst C, Odom DT, Kutter C. The emergence of pirnas against transposon invasion to preserve mammalian genome integrity. Nat Commun. 2017;8(1):1411.

    Article  Google Scholar 

  79. Li C, Ma L, Yu B. Circular rna hsa_circ_0003575 regulates oxldl induced vascular endothelial cells proliferation and angiogenesis. Biomed Pharmacother. 2017;95:1514–9.

    Article  CAS  Google Scholar 

  80. Kang S, Sohn E, Lee S. Hydrogen sulfide as a potential alternative for the treatment of myocardial fibrosis. Oxid Med Cell Longev. 2020;2020:4105382.

    Article  Google Scholar 

  81. Tang C, Zhang M, Huang L, Hu Z, Zhu J, Xiao Z, et al. Circrna_000203 enhances the expression of fibrosis-associated genes by derepressing targets of mir-26b-5p, col1a2 and ctgf, in cardiac fibroblasts. Sci Rep. 2017;7:40342.

    Article  Google Scholar 

  82. Zhu Y, Pan W, Yang T, Meng X, Jiang Z, Tao L, et al. Upregulation of circular rna circnfib attenuates cardiac fibrosis by sponging mir-433. Front Genet. 2019;10:564.

    Article  CAS  Google Scholar 

  83. Ni H, Li W, Zhuge Y, Xu S, Wang Y, Chen Y, et al. Inhibition of circhipk3 prevents angiotensin ii-induced cardiac fibrosis by sponging mir-29b-3p. Int J Cardiol. 2019;292:188–96.

    Article  Google Scholar 

  84. Wang K, Dong Y, Liu J, Qian L, Wang T, Gao X, et al. Effects of redox in regulating and treatment of metabolic and inflammatory cardiovascular diseases. Oxid Med Cell Longev. 2020;2020:5860356.

    Article  Google Scholar 

  85. Costa M, Cortez-Dias N, Gabriel A, de Sousa J, Fiúza M, Gallego J, et al. Circrna-mirna cross-talk in the transition from paroxysmal to permanent atrial fibrillation. Int J Cardiol. 2019;290:134–7.

    Article  Google Scholar 

  86. Jiang S, Guo C, Zhang W, Che W, Zhang J, Zhuang S, et al. The integrative regulatory network of circrna, microrna, and mrna in atrial fibrillation. Front Genet. 2019;10:526.

    Article  CAS  Google Scholar 

  87. Hu X, Chen L, Wu S, Xu K, Jiang W, Qin M, et al. Integrative analysis reveals key circular rna in atrial fibrillation. Front Genet. 2019;10:108.

    Article  CAS  Google Scholar 

  88. Liu T, Zhang G, Wang Y, Rao M, Zhang Y, Guo A, et al. Identification of circular rna-microrna-messenger rna regulatory network in atrial fibrillation by integrated analysis. Biomed Res Int. 2020;2020:8037273.

    Google Scholar 

  89. Zhang P, Sun J, Li W. Genome-wide profiling reveals atrial fibrillation-related circular rnas in atrial appendages. Gene. 2020;728:144286.

    Article  CAS  Google Scholar 

  90. Huang Y, Tang C, Du J, Jin H. Endogenous sulfur dioxide: a new member of gasotransmitter family in the cardiovascular system. Oxid Med Cell Longev. 2016;2016:8961951.

    Article  Google Scholar 

  91. Heagerty A, Heerkens E, Izzard A. Small artery structure and function in hypertension. J Cell Mol Med. 2010;14(5):1037–43.

    Google Scholar 

  92. Yin L, Yao J, Deng G, Wang X, Cai W, Shen J. Identification of candidate lncrnas and circrnas regulating wnt3/β-catenin signaling in essential hypertension. Aging. 2020;12(9):8261–88.

    Article  CAS  Google Scholar 

  93. Wu N, Jin L, Cai J. Profiling and bioinformatics analyses reveal differential circular rna expression in hypertensive patients. Clin Exp Hypertens. 2017;39(5):454–9.

    Article  CAS  Google Scholar 

  94. Bao X, He X, Zheng S, Sun J, Luo Y, Tan R, et al. Up-regulation of circular rna hsa_circ_0037909 promotes essential hypertension. J Clin Lab Anal. 2019;33(4):e22853.

    Article  Google Scholar 

  95. Liu L, Gu T, Bao X, Zheng S, Zhao J, Zhang L. Microarray profiling of circular rna identifies hsa_circ_0126991 as a potential risk factor for essential hypertension. Cytogenet Genome Res. 2019;157(4):203–12.

    Article  CAS  Google Scholar 

  96. Prestes P, Maier M, Woods B, Charchar F. A guide to the short, long and circular rnas in hypertension and cardiovascular disease. Int J Mol Sci. 2020;21(10):3666.

    Article  CAS  Google Scholar 

  97. Wang J, Sun H, Zhou Y, Huang K, Que J, Peng Y, et al. Circular rna microarray expression profile in 3,4-benzopyrene/angiotensin ii-induced abdominal aortic aneurysm in mice. J Cell Biochem. 2019;120(6):10484–94.

    Article  CAS  Google Scholar 

  98. Wilmink A, Quick C. Epidemiology and potential for prevention of abdominal aortic aneurysm. Br J Surg. 1998;85(2):155–62.

    Article  CAS  Google Scholar 

  99. Golledge J, Moxon J, Singh T, Bown M, Mani K, Wanhainen A. Lack of an effective drug therapy for abdominal aortic aneurysm. J Intern Med. 2020;288(1):6–22.

    Article  CAS  Google Scholar 

  100. Yang R, Wang Z, Meng G, Hua L. Circular rna ccdc66 facilitates abdominal aortic aneurysm through the overexpression of ccdc66. Cell Biochem Funct. 2020;38(7):830–8.

    Article  CAS  Google Scholar 

  101. Yue J, Zhu T, Yang J, Si Y, Xu X, Fang Y, et al. Circcbfb-mediated mir-28–5p facilitates abdominal aortic aneurysm via lypd3 and gria4. Life Sci. 2020;253:117533.

    Article  CAS  Google Scholar 

  102. Zheng C, Niu H, Li M, Zhang H, Yang Z, Tian L, et al. Cyclic rna hsa-circ-000595 regulates apoptosis of aortic smooth muscle cells. Mol Med Rep. 2015;12(5):6656–62.

    Article  CAS  Google Scholar 

  103. Chen J, Cui L, Yuan J, Zhang Y, Sang H. Circular rna wdr77 target fgf-2 to regulate vascular smooth muscle cells proliferation and migration by sponging mir-124. Biochem Biophys Res Commun. 2017;494:126–32.

    Article  CAS  Google Scholar 

  104. Mao Y, Wang J, Guo X, Bi Y, Wang C. Circ-satb2 upregulates stim1 expression and regulates vascular smooth muscle cell proliferation and differentiation through mir-939. Biochem Biophys Res Commun. 2018;505(1):119–25.

    Article  CAS  Google Scholar 

  105. Zhou M, Shi Z, Cai L, Li X, Ding Y, Xie T, et al. Circular rna expression profile and its potential regulative role in human abdominal aortic aneurysm. BMC Cardiovasc Disord. 2020;20(1):70.

    Article  CAS  Google Scholar 

  106. Salgado-Somoza A, Zhang L, Vausort M, Devaux Y. The circular rna micra for risk stratification after myocardial infarction. Int J Cardiol Heart Vasc. 2017;17:33–6.

    Google Scholar 

  107. Vausort M, Salgado-Somoza A, Zhang L, Leszek P, Devaux Y. Myocardial infarction-associated circular rna predicting left ventricular dysfunction. J Am Coll Cardiol. 2016;68(11):1247–8.

    Article  Google Scholar 

  108. Zhao Z, Li X, Gao C, Jian D, Hao P, Rao L, et al. Peripheral blood circular rna hsa_circ_0124644 can be used as a diagnostic biomarker of coronary artery disease. Sci Rep. 2017;7:39918.

    Article  CAS  Google Scholar 

  109. Yang Y, Yu T, Jiang S, Zhang Y, Li M, Tang N, et al. Mirnas as potential therapeutic targets and diagnostic biomarkers for cardiovascular disease with a particular focus on wo2010091204. Expert Opin Ther Pat. 2017;27(9):1021–9.

    Article  CAS  Google Scholar 

  110. Bao X, Zheng S, Mao S, Gu T, Liu S, Sun J, et al. A potential risk factor of essential hypertension in case-control study: circular rna hsa_circ_0037911. Biochem Biophys Res Commun. 2018;498(4):789–94.

    Article  CAS  Google Scholar 

  111. Garikipati V, Verma S, Cheng Z, Liang D, Truongcao M, Cimini M, et al. Circular rna circfndc3b modulates cardiac repair after myocardial infarction via fus/vegf-a axis. Nat Commun. 2019;10(1):4317.

    Article  CAS  Google Scholar 

  112. Shen L, Hu Y, Lou J, Yin S, Wang W, Wang Y, et al. Circrna-0044073 is upregulated in atherosclerosis and increases the proliferation and invasion of cells by targeting mir-107. Mol Med Rep. 2019;19(5):3923–32.

    CAS  Google Scholar 

  113. Yang L, Yang F, Zhao H, Wang M, Zhang Y. Circular rna circchfr facilitates the proliferation and migration of vascular smooth muscle via mir-370/foxo1/cyclin d1 pathway. Mol Ther Nucleic Acids. 2019;16:434–41.

    Article  CAS  Google Scholar 

  114. Zhang Y, Chen Y, Yao H, Lie Z, Chen G, Tan H, et al. Elevated serum circ_0068481 levels as a potential diagnostic and prognostic indicator in idiopathic pulmonary arterial hypertension. Pulm Circ. 2019;9(4):2045894019888416.

    Article  Google Scholar 

  115. Zheng S, Gu T, Bao X, Sun J, Zhao J, Zhang T, et al. Circular rna hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension. Exp Ther Med. 2019;17(3):1728–36.

    CAS  Google Scholar 

  116. Liu Y, Yang Y, Wang Z, Fu X, Chu X, Li Y, et al. Insights into the regulatory role of circrna in angiogenesis and clinical implications. Atherosclerosis. 2020;298:14–26.

    Article  CAS  Google Scholar 

  117. Fan X, Weng X, Zhao Y, Chen W, Gan T, Xu D. Circular rnas in cardiovascular disease: an overview. Biomed Res Int. 2017;2017:5135781.

    Article  Google Scholar 

  118. Odqvist M, Andersson P, Tygesen H, Eggers K, Holzmann M. High-sensitivity troponins and outcomes after myocardial infarction. J Am Coll Cardiol. 2018;71(23):2616–24.

    Article  CAS  Google Scholar 

  119. McDonald K, Troughton R, Dahlström U, Dargie H, Krum H, van der Meer P, et al. Daily home bnp monitoring in heart failure for prediction of impending clinical deterioration: results from the home hf study. Eur J Heart Fail. 2018;20(3):474–80.

    Article  CAS  Google Scholar 

  120. Gaggin H, Januzzi J. Biomarkers and diagnostics in heart failure. Biochem Biophys Acta. 2013;1832(12):2442–50.

    CAS  Google Scholar 

  121. Marciniak A, Nawrocka Rutkowska J, Brodowska A, Wiśniewska B, Starczewski A. Cardiovascular system diseases in patients with polycystic ovary syndrome - the role of inflammation process in this pathology and possibility of early diagnosis and prevention. Ann Agric Environ Med. 2016;23(4):537–41.

    Article  CAS  Google Scholar 

  122. Olson J. D-dimer: an overview of hemostasis and fibrinolysis, assays, and clinical applications. Adv Clin Chem. 2015;69:1–46.

    Article  CAS  Google Scholar 

  123. Shan C, Zhang Y, Hao X, Gao J, Chen X, Wang K. Biogenesis, functions and clinical significance of circrnas in gastric cancer. Mol Cancer. 2019;18(1):136.

    Article  Google Scholar 

  124. Boeckel J, Jaé N, Heumüller A, Chen W, Boon R, Stellos K, et al. Identification and characterization of hypoxia-regulated endothelial circular rna. Circ Res. 2015;117(10):884–90.

    Article  CAS  Google Scholar 

  125. Yang J, Cheng M, Gu B, Wang J, Yan S, Xu D. Circrna_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via mir-6089/akt1/nf-κb axis. Cell Death Dis. 2020;11(10):833.

    Article  CAS  Google Scholar 

  126. Fan CY, Lei XJ, Fang ZQ, Jiang QH, Wu FX. Circr2disease: a manually curated database for experimentally supported circular rnas associated with various diseases. Database (Oxford). 2018;2018:bay044.

  127. Yang Q, Du WW, Wu N, Yang W, Awan FM, Fang L, et al. A circular rna promotes tumorigenesis by inducing c-myc nuclear translocation. Cell Death Differ. 2018;24(9):1609–20.

    Article  Google Scholar 

  128. Xia S, Feng J, Lei L, Hu J, Xia L, Wang J, et al. Comprehensive characterization of tissue-specific circular rnas in the human and mouse genomes. Brief Bioinform. 2017;18(6):984–92.

    CAS  Google Scholar 

  129. Li S, Li Y, Chen B, Zhao J, Yu S, Tang Y, et al. Exorbase: a database of circrna, lncrna and mrna in human blood exosomes. Nucleic Acids Res. 2018;46(D1):D106–12.

    Article  CAS  Google Scholar 

  130. Tang Z, Li ZX, Zhao J, Qian F, Feng C, Li Y, et al. Trcirc: a resource for transcriptional regulation information of circrnas. Brief Bioinform. 2019;20(6):2327–33.

    Article  CAS  Google Scholar 

  131. Meng XW, Hu DH, Zhang PJ, Chen Q, Chen M. Circfunbase: a database for functional circular rnas. Database (Oxford). 2019;2019:6.

  132. Dudekula DB, Panda AC, Grammatikakis I, De S, Abdelmohsen K, Gorospe M. Circinteractome: a web tool for exploring circular rnas and their interacting proteins and micrornas. RNA Biol. 2016;13(1):34–42.

    Article  Google Scholar 

  133. Zhao S, Li S, Liu W, Wang Y, Li X, Zhu S, et al. Circular rna signature in lung adenocarcinoma: a mioncocirc database-based study and literature review. Front Oncol. 2020;10:523342.

    Article  Google Scholar 

  134. Ghosal S, Das S, Sen R, Basak P, Chakrabarti J. Circ2traits: a comprehensive database for circular rna potentially associated with disease and traits. Front Genet. 2013;4:283.

    Article  Google Scholar 

  135. Wu S, Liu H, Huang P, Chang I, Lee C, Yang C, et al. Circlncrnanet: an integrated web-based resource for mapping functional networks of long or circular forms of noncoding rnas. GigaScience. 2018;7(1):1–10.

    Google Scholar 

  136. Liu M, Wang Q, Shen J, Yang BB, Ding X. Circbank: a comprehensive database for circrna with standard nomenclature. RNA Biol. 2019;16(7):899–905.

    Article  Google Scholar 

  137. Liu YC, Li JR, Sun CH, Andrews E, Chao RF, Lin FM, et al. Circnet: a database of circular rnas derived from transcriptome sequencing data. Nucleic Acids Res. 2016;44(D1):D209–15.

    Article  CAS  Google Scholar 

  138. Wu W, Ji P, Zhao F. Circatlas: An integrated resource of one million highly accurate circular rnas from 1070 vertebrate transcriptomes. Genome Biol. 2020;21(1):101.

    Article  CAS  Google Scholar 

  139. Zheng L, Li J, Wu J, Sun W, Liu S, Wang Z, et al. Deepbase v2.0: identification, expression, evolution and function of small rnas, lncrnas and circular rnas from deep-sequencing data. Nucleic Acids Res. 2016;44(D1):D196-202.

    Article  CAS  Google Scholar 

  140. Zhong S, Wang J, Zhang Q, Xu H, Feng J. Circprimer: a software for annotating circrnas and determining the specificity of circrna primers. BMC Bioinformatics. 2018;19(1):292.

    Article  Google Scholar 

  141. Dong R, Ma X, Li G, Yang L. Circpedia v2: an updated database for comprehensive circular rna annotation and expression comparison. Genomics Proteomics Bioinformatics. 2018;16(4):226–33.

    Article  Google Scholar 

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Acknowledgements

We thank Professor Kun Wang, the head of the Heart Development Center, and Professor Peifeng Li, the head of translational research, who provided substantial scientific support to this work.

Funding

This work was supported by the National Natural Science Foundation of China (81870236, 82070313, 81770275), Taishan Scholar Programme of Shandong Province, Major Research Programme of the National Natural Science Foundation of China (No. 91849209) and Qingdao Scientific Programme (No. 18–6-1–63-nsh).

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  1. Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, 266021, Shandong, China

    Kai Wang, Xiang-Qian Gao, Tao Wang & Lu-Yu Zhou

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  1. Kai Wang
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Lu-Yu Zhou, Kai Wang, Xiang-Qian Gao and Tao Wang provided direction and guidance throughout the preparation of this manuscript. Kai Wang drafted the manuscript. Lu-Yu Zhou reviewed and made significant revisions to the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Lu-Yu Zhou.

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Wang, K., Gao, XQ., Wang, T. et al. The Function and Therapeutic Potential of Circular RNA in Cardiovascular Diseases. Cardiovasc Drugs Ther 37, 181–198 (2023). https://doi.org/10.1007/s10557-021-07228-5

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