The Emerging Role of CircRNAs in Atherosclerosis

Jing      Yang; Shuling      Rong
Abstract

Cardiovascular diseases (CVDs) based on atherosclerosis remain the main reason for death in Western countries and China. Cardiovascular research has demonstrated that its pathogenesis is closely associated with endothelial cell (EC) injury, the phenotypic transformation of vascular smooth muscle cells (VSMCs), and the abnormal biological behaviour of macrophages. In recent years, circular RNAs (circRNAs) have received much attention for their unique role in the pathogenesis of atherosclerosis. In this review, we discussed the mechanisms associated with ECs, VSMCs, and macrophages in atherosclerosis and summarized the role of circRNAs in atherosclerosis. This review aims to provide a basis for the prevention and treatment of atherosclerosis.
Graphical Abstract

[1]
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med  2005; 352(16): 1685-95.
 [http://dx.doi.org/10.1056/NEJMra043430] [PMID:  15843671]

[2]
Li Z, Tang H, Tu Y. Molecular and nonmolecular imaging of macrophages in atherosclerosis. Front Cardiovasc Med  2021; 8670639
 [http://dx.doi.org/10.3389/fcvm.2021.670639] [PMID:  34095259]

[3]
Hua Y, Zhang J, Liu Q, et al. The induction of endothelial autophagy and its role in the development of atherosclerosis. Front Cardiovasc Med  2022; 9831847
 [http://dx.doi.org/10.3389/fcvm.2022.831847] [PMID:  35402552]

[4]
Wang X, Liang Z, Xiang H, Li Y, Chen S, Lu H. LKB1 regulates vascular macrophage functions in atherosclerosis. Front Pharmacol  2021; 12810224
 [http://dx.doi.org/10.3389/fphar.2021.810224] [PMID:  34975507]

[5]
Lei Y, Xu J, Li M, et al. MIA SH3 Domain ER export factor 3 deficiency prevents neointimal formation by restoring bat-like PVAT and decreasing VSMC proliferation and migration. Front Endocrinol (Lausanne)  2021; 12748216
 [http://dx.doi.org/10.3389/fendo.2021.748216] [PMID:  34858331]

[6]
Qin B, Shu Y, Long L, et al. MicroRNA-142-3p induces atherosclerosis-associated endothelial cell apoptosis by directly targeting rictor. Cell Physiol Biochem  2018; 47(4): 1589-603.
 [http://dx.doi.org/10.1159/000490932] [PMID:  29949787]

[7]
Jensen HA, Mehta JL. Endothelial cell dysfunction as a novel therapeutic target in atherosclerosis. Expert Rev Cardiovasc Ther  2016; 14(9): 1021-33.
 [http://dx.doi.org/10.1080/14779072.2016.1207527] [PMID:  27362558]

[8]
Ladak SS, McQueen LW, Layton GR, Aujla H, Adebayo A, Zakkar M. The role of endothelial cells in the onset, development and modulation of vein graft disease. Cells  2022; 11(19): 3066.
 [http://dx.doi.org/10.3390/cells11193066] [PMID:  36231026]

[9]
Matsuzawa Y, Lerman A. Endothelial dysfunction and coronary artery disease. Coron Artery Dis  2014; 25(8): 713-24.
 [http://dx.doi.org/10.1097/MCA.0000000000000178] [PMID:  25365643]

[10]
Sun HJ, Wu ZY, Nie XW, Bian JS. Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front Pharmacol  2020; 10: 1568.
 [http://dx.doi.org/10.3389/fphar.2019.01568] [PMID:  32038245]

[11]
Medina-Leyte DJ, Domínguez-Pérez M, Mercado I, Villarreal-Molina MT, Jacobo-Albavera L. Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a model to study cardiovascular disease: A review. Appl Sci (Basel)  2020; 10(3): 938.
 [http://dx.doi.org/10.3390/app10030938]

[12]
Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: A dynamic balance. Nat Rev Immunol  2013; 13(10): 709-21.
 [http://dx.doi.org/10.1038/nri3520] [PMID:  23995626]

[13]
Ginhoux F, Jung S. Monocytes and macrophages: Developmental pathways and tissue homeostasis. Nat Rev Immunol  2014; 14(6): 392-404.
 [http://dx.doi.org/10.1038/nri3671] [PMID:  24854589]

[14]
Poznyak AV, Nikiforov NG, Starodubova AV, Popkova TV, Orekhov AN. Macrophages and foam cells: Brief overview of their role, linkage, and targeting potential in atherosclerosis. Biomedicines  2021; 9(9): 1221.
 [http://dx.doi.org/10.3390/biomedicines9091221] [PMID:  34572406]

[15]
Javadifar A, Rastgoo S, Banach M, Jamialahmadi T, Johnston TP, Sahebkar A. Foam cells as therapeutic targets in atherosclerosis with a focus on the regulatory roles of non-coding RNAs. Int J Mol Sci  2021; 22(5): 2529.
 [http://dx.doi.org/10.3390/ijms22052529] [PMID:  33802600]

[16]
Randolph GJ. Mechanisms that regulate macrophage burden in atherosclerosis. Circ Res  2014; 114(11): 1757-71.
 [http://dx.doi.org/10.1161/CIRCRESAHA.114.301174] [PMID:  24855200]

[17]
Liu Y, Yuan P, Wu J, Hu B. Lipid accumulation and novel insight into vascular smooth muscle cells in atherosclerosis. J Mol Med (Berl)  2021; 99(11): 1511-26.
 [http://dx.doi.org/10.1007/s00109-021-02109-8] [PMID:  34345929]

[18]
Wang X, Li H, Zhang Y, et al. Suppression of miR-4463 promotes phenotypic switching in VSMCs treated with Ox-LDL. Cell Tissue Res  2021; 383(3): 1155-65.
 [http://dx.doi.org/10.1007/s00441-020-03338-y] [PMID:  33245416]

[19]
Pan J, Cai Y, Liu M, Li Z. Role of vascular smooth muscle cell phenotypic switching in plaque progression: A hybrid modeling study. J Theor Biol  2021; 526110794
 [http://dx.doi.org/10.1016/j.jtbi.2021.110794] [PMID:  34087268]

[20]
Chistiakov DA, Orekhov AN, Bobryshev YV. Vascular smooth muscle cell in atherosclerosis. Acta Physiol (Oxf)  2015; 214(1): 33-50.
 [http://dx.doi.org/10.1111/apha.12466] [PMID:  25677529]

[21]
Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness. Cardiovasc Res  2018; 114(4): 590-600.
 [http://dx.doi.org/10.1093/cvr/cvy010] [PMID:  29514202]

[22]
Djebali S, Davis CA, Merkel A, et al. Landscape of transcription in human cells. Nature  2012; 489(7414): 101-8.
 [http://dx.doi.org/10.1038/nature11233] [PMID:  22955620]

[23]
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature  2013; 495(7441): 333-8.
 [http://dx.doi.org/10.1038/nature11928] [PMID:  23446348]

[24]
Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet  2019; 20(11): 675-91.
 [http://dx.doi.org/10.1038/s41576-019-0158-7] [PMID:  31395983]

[25]
Zhang Z, Zhang T, Feng R, Huang H, Xia T, Sun C. circARF3 alleviates mitophagy-mediated inflammation by targeting miR-103/TRAF3 in mouse adipose tissue. Mol Ther Nucleic Acids  2019; 14: 192-203.
 [http://dx.doi.org/10.1016/j.omtn.2018.11.014] [PMID:  30623853]

[26]
Han B, Zhang Y, Zhang Y, et al. Novel insight into circular RNA HECTD1 in astrocyte activation via autophagy by targeting MIR142 -TIPARP: Implications for cerebral ischemic stroke. Autophagy  2018; 14(7): 1164-84.
 [http://dx.doi.org/10.1080/15548627.2018.1458173] [PMID:  29938598]

[27]
Li M, Ding W, Sun T, et al. Biogenesis of circular RNA s and their roles in cardiovascular development and pathology. FEBS J  2018; 285(2): 220-32.
 [http://dx.doi.org/10.1111/febs.14191] [PMID:  28783257]

[28]
Ghafouri-Fard S, Gholipour M, Taheri M. The emerging role of long non-coding RNAs and circular RNAs in coronary artery disease. Front Cardiovasc Med  2021; 8632393
 [http://dx.doi.org/10.3389/fcvm.2021.632393] [PMID:  33708807]

[29]
Huang X, Zhao Y, Zhou H, Li Y. Circular RNAs in atherosclerosis. Clin Chim Acta  2022; 531: 71-80.
 [http://dx.doi.org/10.1016/j.cca.2022.03.016] [PMID:  35339453]

[30]
Chen LL. The biogenesis and emerging roles of circular RNAs 2013.

[31]
Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO, Moran JV. Cell-type specific features of circular RNA expression. PLoS Genet  2013; 9(9)e1003777
 [http://dx.doi.org/10.1371/journal.pgen.1003777] [PMID:  24039610]

[32]
Qu S, Yang X, Li X, et al. Circular RNA: A new star of noncoding RNAs. Cancer Lett  2015; 365(2): 141-8.
 [http://dx.doi.org/10.1016/j.canlet.2015.06.003] [PMID:  26052092]

[33]
Liu Y, Yang Y, Wang Z, et al. Insights into the regulatory role of circRNA in angiogenesis and clinical implications. Atherosclerosis  2020; 298: 14-26.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2020.02.017] [PMID:  32131039]

[34]
Hou LD, Zhang J. Circular RNAs: An emerging type of RNA in cancer. Int J Immunopathol Pharmacol  2017; 30(1): 1-6.
 [http://dx.doi.org/10.1177/0394632016686985] [PMID:  28134598]

[35]
Wang J, Zhu M, Pan J, Chen C, Xia S, Song Y. Circular RNAs: A rising star in respiratory diseases. Respir Res  2019; 20(1): 3.
 [http://dx.doi.org/10.1186/s12931-018-0962-1] [PMID:  30611252]

[36]
Hu W, Bi ZY, Chen ZL, et al. Emerging landscape of circular RNAs in lung cancer. Cancer Lett  2018; 427: 18-27.
 [http://dx.doi.org/10.1016/j.canlet.2018.04.006] [PMID:  29653267]

[37]
Lan PH, Liu ZH, Pei YJ, et al. Landscape of RNAs in human lumbar disc degeneration. Oncotarget  2016; 7(39): 63166-76.
 [http://dx.doi.org/10.18632/oncotarget.11334] [PMID:  27542248]

[38]
Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell  2013; 51(6): 792-806.
 [http://dx.doi.org/10.1016/j.molcel.2013.08.017] [PMID:  24035497]

[39]
Ju H, Hu Z, Wei D, et al. A novel intronic circular RNA, circGNG7, inhibits head and neck squamous cell carcinoma progression by blocking the phosphorylation of heat shock protein 27 at Ser78 and Ser82. Cancer Commun (Lond)  2021; 41(11): 1152-72.
 [http://dx.doi.org/10.1002/cac2.12213] [PMID:  34498800]

[40]
Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol  2015; 22(3): 256-64.
 [http://dx.doi.org/10.1038/nsmb.2959] [PMID:  25664725]

[41]
Yu J, Xu Q, Wang Z, et al. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol  2018; 68(6): 1214-27.
 [http://dx.doi.org/10.1016/j.jhep.2018.01.012] [PMID:  29378234]

[42]
Gao Y, Wang J, Zhao F. CIRI: An efficient and unbiased algorithm for de novo circular RNA identification. Genome Biol  2015; 16(1): 4.
 [http://dx.doi.org/10.1186/s13059-014-0571-3] [PMID:  25583365]

[43]
Schmidt CA, Matera AG. tRNA introns: Presence, processing, and purpose. Wiley Interdiscip Rev RNA  2020; 11(3)e1583
 [http://dx.doi.org/10.1002/wrna.1583] [PMID:  31883233]

[44]
Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J  2011; 30(21): 4414-22.
 [http://dx.doi.org/10.1038/emboj.2011.359] [PMID:  21964070]

[45]
Ma J, Du WW, Zeng K, et al. An antisense circular RNA circSCRIB enhances cancer progression by suppressing parental gene splicing and translation. Mol Ther  2021; 29(9): 2754-68.
 [http://dx.doi.org/10.1016/j.ymthe.2021.08.002] [PMID:  34365033]

[46]
Du WW, Zhang C, Yang W, Yong T, Awan FM, Yang BB. Identifying and characterizing circRNA-protein interaction. Theranostics  2017; 7(17): 4183-91.
 [http://dx.doi.org/10.7150/thno.21299] [PMID:  29158818]

[47]
Xu G, Watanabe T, Iso Y, et al. Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis. Circ Res  2009; 105(5): 500-10.
 [http://dx.doi.org/10.1161/CIRCRESAHA.109.193870] [PMID:  19644050]

[48]
Ryu J, Kwon DH, Choe N, et al. Characterization of circular RNAs in vascular smooth muscle cells with vascular calcification 2020.
 [http://dx.doi.org/10.1016/j.omtn.2019.11.001]

[49]
Lu X, Liu Y, Xuan W, et al. Circ_1639 induces cells inflammation responses by sponging miR-122 and regulating TNFRSF13C expression in alcoholic liver disease. Toxicol Lett  2019; 314: 89-97.
 [http://dx.doi.org/10.1016/j.toxlet.2019.07.021] [PMID:  31325635]

[50]
Li Z, Huang C, Bao C, et al. Erratum: Corrigendum: Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol  2017; 24(2): 194.
 [http://dx.doi.org/10.1038/nsmb0217-194a] [PMID:  28170000]

[51]
Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res  2017; 27(5): 626-41.
 [http://dx.doi.org/10.1038/cr.2017.31]

[52]
Du WW, Xu J, Yang W, et al. A neuroligin isoform translated by circnlgn contributes to cardiac remodeling. Circ Res  2021; 129(5): 568-82.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.318364] [PMID:  34261347]

[53]
Abe N, Matsumoto K, Nishihara M, et al. Rolling circle translation of circular RNA in living human cells. Sci Rep  2015; 5(1): 16435.
 [http://dx.doi.org/10.1038/srep16435] [PMID:  26553571]

[54]
Conlon Erin G, Manley James L. RNA-binding proteins in neurodegeneration: Mechanisms in aggregate. 

[55]
Du WW, Yang W, Chen Y, 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.
 [PMID:  26873092]

[56]
Holdt LM, Stahringer A, Sass K, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun  2016; 7(1): 12429.
 [http://dx.doi.org/10.1038/ncomms12429] [PMID:  27539542]

[57]
Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell  2014; 56(1): 55-66.
 [http://dx.doi.org/10.1016/j.molcel.2014.08.019]

[58]
Ji Y, Cheng M. GW26-e1483 aberrant expression of circular RNAs in endothelial dysfunction. J Am Coll Cardiol  2015; 66(16): C31.
 [http://dx.doi.org/10.1016/j.jacc.2015.06.1145]

[59]
Li CY, Ma L, Yu B. Circular RNA hsa_circ_0003575 regulates oxLDL induced vascular endothelial cells proliferation and angiogenesis. Biomed Pharmacother  2017; 95: 1514-9.
 [http://dx.doi.org/10.1016/j.biopha.2017.09.064] [PMID:  28946214]

[60]
Jin G, Wang Q, Hu X, et al. Profiling and functional analysis of differentially expressed circular RNAs in high glucose‐induced human umbilical vein endothelial cells. FEBS Open Bio  2019; 9(9): 1640-51.
 [http://dx.doi.org/10.1002/2211-5463.12709] [PMID:  31369204]

[61]
Li H, Liu X, Sun N, et al. Differentially expressed circular non-coding RNAs in atherosclerotic aortic vessels and their potential functions in endothelial injury. Front Cardiovasc Med  2021; 8657544
 [http://dx.doi.org/10.3389/fcvm.2021.657544] [PMID:  34307490]

[62]
Tian J, Fu Y, Li Q, et al. Differential expression and bioinformatics analysis of CircRNA in PDGF-BB-induced vascular smooth muscle cells. Front Genet  2020; 11: 530.
 [http://dx.doi.org/10.3389/fgene.2020.00530] [PMID:  32547599]

[63]
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.
 [http://dx.doi.org/10.1016/j.omtn.2019.02.028] [PMID:  31048182]

[64]
Wang L, Zheng Z, Feng X, et al. circRNA/lncRNA-miRNA-mRNA network in oxidized, low-density, lipoprotein-induced foam cells. DNA Cell Biol  2019; 38(12): 1499-511.
 [http://dx.doi.org/10.1089/dna.2019.4865] [PMID:  31804889]

[65]
Wang Y-W, Shang F-F, Liu W, et al. Novel circular RNAs expressed in brain microvascular endothelial cells after oxygen-glucose deprivation/recovery. Neural Regen Res  2019; 14(12): 2104-11.
 [http://dx.doi.org/10.4103/1673-5374.262589] [PMID:  31397348]

[66]
Peng W, Li T, Pi S, Huang L, Liu Y. Suppression of circular RNA circDHCR24 alleviates aortic smooth muscle cell proliferation and migration by targeting miR-149-5p/MMP9 axis. Biochem Biophys Res Commun  2020; 529(3): 753-9.
 [http://dx.doi.org/10.1016/j.bbrc.2020.06.067] [PMID:  32736703]

[67]
Wang L, Shen C, Wang Y, et al. Identification of circular RNA Hsa_circ_0001879 and Hsa_circ_0004104 as novel biomarkers for coronary artery disease. Atherosclerosis  2019; 286: 88-96.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2019.05.006] [PMID:  31103880]

[68]
Chen W, Lin J, Li B, et al. Screening and functional prediction of differentially expressed circRNAs in proliferative human aortic smooth muscle cells. J Cell Mol Med  2020; 24(8): 4762-72.
 [http://dx.doi.org/10.1111/jcmm.15150] [PMID:  32155686]

[69]
Liu Z, Lou Y, Cui JC, et al. Circular RNA UVRAG mediated by alternative splicing factor NOVA1 regulates adhesion and migration of vascular smooth muscle cells. Genes (Basel)  2021; 12(3): 418.
 [http://dx.doi.org/10.3390/genes12030418] [PMID:  33799408]

[70]
Zhang F, Zhang R, Zhang X, et al. Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits. Aging  2018; 10(9): 2266-83.
 [http://dx.doi.org/10.18632/aging.101541] [PMID:  30187887]

[71]
Pan R-Y, Zhao C-H, Yuan J-X, et al. Circular RNA profile in coronary artery disease. Am J Transl Res  2019; 11(11): 7115-25.
 [PMID:  31814914]

[72]
Liang B, Li M, Deng Q, et al. CircRNA ZNF609 in peripheral blood leukocytes acts as a protective factor and a potential biomarker for coronary artery disease. Ann Transl Med  2020; 8(12): 741.
 [http://dx.doi.org/10.21037/atm-19-4728] [PMID:  32647666]

[73]
Vilades D, Martínez-Camblor P, Ferrero-Gregori A, et al. Plasma circular RNA hsa_circ_0001445 and coronary artery disease: Performance as a biomarker. FASEB J  2020; 34(3): 4403-14.
 [http://dx.doi.org/10.1096/fj.201902507R] [PMID:  31999007]

[74]
Li S, Hu W, Deng F, et al. Identification of circular RNA hsa_circ_0001599 as a novel biomarker for large-artery atherosclerotic stroke. DNA Cell Biol  2021; 40(3): 457-68.
 [http://dx.doi.org/10.1089/dna.2020.5662] [PMID:  33493415]

[75]
Xiao Q, Hou R, Li H, et al. Circulating exosomal circRNAs contribute to potential diagnostic value of large artery atherosclerotic stroke. Front Immunol  2022; 12830018
 [http://dx.doi.org/10.3389/fimmu.2021.830018] [PMID:  35095932]

[76]
Zhang S, Song G, Yuan J, et al. RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis. J Biomed Sci  2020; 27(1): 11.
 [http://dx.doi.org/10.1186/s12929-019-0595-9] [PMID:  31900142]

[77]
Zhang B, Zhang Y, Li R, Li Y, Yan W. Knockdown of circular RNA hsa_circ_0003204 inhibits oxidative stress and apoptosis through the miR-330-5p/Nod2 axis to ameliorate endothelial cell injury induced by low-density lipoprotein. Cent Eur J Immunol  2021; 46(2): 140-51.
 [http://dx.doi.org/10.5114/ceji.2021.108174] [PMID:  34764783]

[78]
Wan H, You T, Luo W. Regulates cell growth, oxidative stress, and inflammation in ox-ldl-induced vascular endothelial cells via regulating miR-942-5p/HDAC9 axis. Front Cardiovasc Med  2021; 8646832
 [http://dx.doi.org/10.3389/fcvm.2021.646832] [PMID:  33869307]

[79]
Qiuxia S, Xianhua D, Chonghui T, Xiaojie W, Youguo H, Jun W. Knockdown of circ_0003204 alleviates oxidative low-density lipoprotein-induced human umbilical vein endothelial cells injury: Circulating RNAs could explain atherosclerosis disease progression. Open Med  2021; 16(1)

[80]
Zhang D, Zhang G, Yu K, Zhang X, Jiang A. Circ_0003204 knockdown protects endothelial cells against oxidized low-density lipoprotein- induced injuries by targeting the miR-491-5p-ICAM1 pathway. Journal of thrombosis and thrombolysis 

[81]
Peng K, Jiang P, Du Y, Zeng D, Wu J. Oxidized lowヾensity lipoprotein accelerates the injury of endothelial cells via circ︰SP36 / miR / VCAM1 axis International Union of Biochemistry and Molecular Biology Life  2020; 73(1)

[82]
Miao J, Wang B, Shao R, Wang Y. CircUSP36 knockdown alleviates oxidized low density lipoprotein induced cell injury and inflammatory responses in human umbilical vein endothelial cells via the miR 20a 5p/ROCK2 axis. Int J Mol Med  2021; 47(4): 40.
 [http://dx.doi.org/10.3892/ijmm.2021.4873] [PMID:  33576448]

[83]
JianGuo H, Xia T, JiangJie W, Jia L, Ping C, Yan S. A circular RNA, circUSP36, accelerates endothelial cell dysfunction in atherosclerosis by adsorbing miR-637 to enhance WNT4 expression. Bioengineered  2021; 12(1)

[84]
Wang G, Li Y, Liu Z, et al. Circular RNA circ_0124644 exacerbates the ox-LDL-induced endothelial injury in human vascular endothelial cells through regulating PAPP-A by acting as a sponge of miR-149-5p. Mol Cell Biochem  2020; 471(1-2): 51-61.
 [http://dx.doi.org/10.1007/s11010-020-03764-0] [PMID:  32500475]

[85]
Shao X, Liu Z, Liu S, Lin N, Deng Y. Astragaloside IV alleviates atherosclerosis through targeting circ_0000231/miR-135a-5p/CLIC4 axis in AS cell model in vitro. Mol Cell Biochem  2021; 476(4): 1783-95.
 [http://dx.doi.org/10.1007/s11010-020-04035-8] [PMID:  33439448]

[86]
Fong GH. Potential contributions of intimal and plaque hypoxia to atherosclerosis. Curr Atheroscler Rep  2015; 17(6): 32.
 [http://dx.doi.org/10.1007/s11883-015-0510-0] [PMID:  25876920]

[87]
Liu C, Yao MD, Li CP, et al. Silencing of circular RNA-ZNF609 ameliorates vascular endothelial dysfunction. Theranostics  2017; 7(11): 2863-77.
 [http://dx.doi.org/10.7150/thno.19353] [PMID:  28824721]

[88]
Wang H, Yan H, Wang C, et al. circAFF1 aggravates vascular endothelial cell dysfunction mediated by miR-516b/SAV1/YAP1 axis. Front Physiol  2020; 11: 899.
 [http://dx.doi.org/10.3389/fphys.2020.00899] [PMID:  32848851]

[89]
Yuan T, Yang T, Chen H, et al. New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. Redox Biol  2019; 20: 247-60.
 [http://dx.doi.org/10.1016/j.redox.2018.09.025] [PMID:  30384259]

[90]
Cheng J, Liu Q, Hu N, et al. Downregulation of hsa_circ_0068087 ameliorates TLR4/NF-κB/NLRP3 inflammasome-mediated inflammation and endothelial cell dysfunction in high glucose conditioned by sponging miR-197. Gene  2019; 709: 1-7.
 [http://dx.doi.org/10.1016/j.gene.2019.05.012] [PMID:  31108165]

[91]
Zhang W, Sui Y. CircBPTF knockdown ameliorates high glucose-induced inflammatory injuries and oxidative stress by targeting the miR-384/LIN28B axis in human umbilical vein endothelial cells. Mol Cell Biochem  2020; 471(1-2): 101-11.
 [http://dx.doi.org/10.1007/s11010-020-03770-2] [PMID:  32524321]

[92]
Wu W, Zhou M, Liu D, et al. circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression. Mol Ther Nucleic Acids  2021; 26: 374-87.
 [http://dx.doi.org/10.1016/j.omtn.2021.07.020] [PMID:  34552819]

[93]
Gao Y, Li G, Fan S, et al. Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox‐LDL‐induced endothelial dysfunction in atherosclerosis by functioning as a miR‐876‐3p sponge. Clin Exp Pharmacol Physiol  2021; 48(8): 1137-49.
 [http://dx.doi.org/10.1111/1440-1681.13504] [PMID:  33844344]

[94]
Wei Z, Ran H, Yang C. CircRSF1 contributes to endothelial cell growth, migration and tube formation under ox-LDL stress through regulating miR-758/CCND2 axis. Life Sci  2020; 259118241
 [http://dx.doi.org/10.1016/j.lfs.2020.118241] [PMID:  32791147]

[95]
Tiliwaldi H, Tursun A, Tohti A, Mamatzunun M, Wu Z. Circ_0000345 protects endothelial cells from oxidized low-density lipoprotein-induced injury by miR-129-5p/ten-eleven translocation axis. J Cardiovasc Pharmacol  2021; 77(5): 603-13.
 [PMID:  33951697]

[96]
Liang G, Chen S, Xin S, Dong L. Overexpression of hsa_circ_0001445 reverses oxLDL induced inhibition of HUVEC proliferation via SRSF1. Mol Med Rep  2021; 24(1): 507.
 [http://dx.doi.org/10.3892/mmr.2021.12146] [PMID:  33982782]

[97]
Fudong H, Xi C, Juan G, Yangyang S, Jinhua Y. CircDIP2C ameliorates oxidized low-density lipoprotein-induced cell dysfunction by binding to miR-556-5p to induce TET2 in human umbilical vein endothelial cells. Vascular pharmacology 2021.

[98]
Wang Y, Zhao R, Liu W, et al. Exosomal circHIPK3 released from hypoxia-pretreated cardiomyocytes regulates oxidative damage in cardiac microvascular endothelial cells via the miR-29a/IGF-1 pathway. Oxid Med Cell Longev  2019; 2019: 1-28.
 [http://dx.doi.org/10.1155/2019/7954657] [PMID:  31885817]

[99]
Boeckel JN, Jaé N, Heumüller AW, et al. Identification and characterization of hypoxia-regulated endothelial circular RNA. Circ Res  2015; 117(10): 884-90.
 [http://dx.doi.org/10.1161/CIRCRESAHA.115.306319] [PMID:  26377962]

[100]
Dang RY, Liu FL, 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.
 [http://dx.doi.org/10.1016/j.bbrc.2017.05.164] [PMID:  28571741]

[101]
Pan L, Lian W, Zhang X, et al. Human circular RNA 0054633 regulates high glucose induced vascular endothelial cell dysfunction through the microRNA 218/roundabout 1 and microRNA 218/heme oxygenase 1 axes. Int J Mol Med  2018; 42(1): 597-606.
 [http://dx.doi.org/10.3892/ijmm.2018.3625] [PMID:  29693114]

[102]
Zhang Q, Long J, Li N, Ma X, Zheng L. Circ_CLASP2 regulates high glucose-induced dysfunction of human endothelial cells through targeting miR-140-5p/FBXW7 axis. Front Pharmacol  2021; 12594793
 [http://dx.doi.org/10.3389/fphar.2021.594793] [PMID:  33776760]

[103]
Cao Y, Yuan G, Zhang Y, Lu R. High glucose-induced circHIPK3 downregulation mediates endothelial cell injury. Biochem Biophys Res Commun  2018; 507(1-4): 362-8.
 [http://dx.doi.org/10.1016/j.bbrc.2018.11.041] [PMID:  30454897]

[104]
Wang M, Li C, Cai T, Zhang A, Cao J, Xin H. Circ_CHFR promotes platelet-derived growth factor-bb–induced proliferation, invasion, and migration in vascular smooth muscle cells via the miR-149-5p/NRP2 axis. J Cardiovasc Pharmacol  2022; 79(1): e94-e102.
 [http://dx.doi.org/10.1097/FJC.0000000000001055] [PMID:  33990513]

[105]
Zheng X, Liu J, Gong X, Zhang X, Ma S. Circ_0002984 enhances growth, invasion, and migration in PDGF-bb–induced vascular smooth muscle cells through miR-379-5p/FRS2 axis. J Cardiovasc Pharmacol  2021; 78(6): 875-84.
 [http://dx.doi.org/10.1097/FJC.0000000000001143] [PMID:  34882114]

[106]
Fan K, Ruan X, Wang L, Lu W, Shi Q, Xu Y. Circ_0004872 promotes platelet-derived growth factor-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs via miR-513a-5p/TXNIP axis. Vascul Pharmacol  2021; 140106842
 [http://dx.doi.org/10.1016/j.vph.2021.106842] [PMID:  33592319]

[107]
Huang Z, Li P, Wu L, et al. Hsa_circ_0029589 knockdown inhibits the proliferation, migration and invasion of vascular smooth muscle cells via regulating miR-214-3p and STIM1. Life Sci  2020; 259118251
 [http://dx.doi.org/10.1016/j.lfs.2020.118251] [PMID:  32795540]

[108]
Lu Q, Li Y, Lou J, Li P, Gu Y, Wang X. Circ-CHFR modulates the proliferation, migration, and invasion of ox-LDL-induced human aorta vascular smooth muscle cells through the miR-214-3p/PAPPA axis. Clin Hemorheol Microcirc  2022; 80(4): 399-412.
 [http://dx.doi.org/10.3233/CH-211288] [PMID:  34842180]

[109]
Hou X, Dai H, Zheng Y. Circular RNA hsa_circ_0008896 accelerates atherosclerosis by promoting the proliferation, migration and invasion of vascular smooth muscle cells via hsa-miR-633/CDC20B (cell division cycle 20B) axis. Bioengineered  2022; 13(3): 5987-98.
 [http://dx.doi.org/10.1080/21655979.2022.2039467] [PMID:  35212610]

[110]
Kou L, Yang N, Dong B, et al. Circular RNA testis-expressed 14 overexpression induces apoptosis and suppresses migration of ox-LDL-stimulated vascular smooth muscle cells via regulating the microRNA 6509-3p/thanatos-associated domain-containing apoptosis-associated protein 1 axis. Bioengineered  2022; 13(5): 13150-61.
 [http://dx.doi.org/10.1080/21655979.2022.2070582] [PMID:  35635088]

[111]
Ding P, Ding Y, Tian Y, Lei X. Circular RNA circ_0010283 regulates the viability and migration of oxidized low density lipoprotein induced vascular smooth muscle cells via an miR 370 3p/HMGB1 axis in atherosclerosis. Int J Mol Med  2020; 46(4): 1399-408.
 [http://dx.doi.org/10.3892/ijmm.2020.4703] [PMID:  32945389]

[112]
Feng Z, Zhu Y, Zhang J, Yang W, Chen Z, Li B. Hsa-circ_0010283 regulates oxidized low-density lipoprotein-induced proliferation and migration of vascular smooth muscle cells by targeting the miR-133a-3p/pregnancy-associated plasma protein A axis. Circ J  2020; 84(12): 2259-69.
 [http://dx.doi.org/10.1253/circj.CJ-20-0345] [PMID:  33162460]

[113]
Yu H, Zhao L, Zhao Y, Fei J, Zhang W. Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis. Vascul Pharmacol  2020; 135106782
 [http://dx.doi.org/10.1016/j.vph.2020.106782] [PMID:  32860985]

[114]
Zhang Y, Zhang C, Chen Z, Wang M. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis. Open Life Sci  2021; 16(1): 419-30.
 [http://dx.doi.org/10.1515/biol-2021-0044] [PMID:  33981849]

[115]
Li X, Li L, Dong X, Ding J, Ma H, Han W. Circ_GRN promotes the proliferation, migration, and inflammation of vascular smooth muscle cells in atherosclerosis through miR-214-3p/FOXO1 axis. J Cardiovasc Pharmacol  2021; 77(4): 470-9.
 [http://dx.doi.org/10.1097/FJC.0000000000000982] [PMID:  33818550]

[116]
Zhao Q, Lu Y-H, Wang X, Zhang X-J. Circ_USP36/miR-182-5p/KLF5 axis regulates the ox-LDL-induced injury in human umbilical vein smooth muscle cells. Am J Transl Res  2020; 12(12): 7855-69.
 [PMID:  33437365]

[117]
Zhang LL. CircRNA-PTPRA promoted the progression of atherosclerosis through sponging with miR-636 and upregulating the transcription factor SP1. Eur Rev Med Pharmacol Sci  2020; 24(23): 12437-49.
 [PMID:  33336764]

[118]
Sun J, Zhang Z, Yang S. Circ_RUSC2 upregulates the expression of miR-661 target gene SYK and regulates the function of vascular smooth muscle cells. Biochem Cell Biol  2019; 97(6): 709-14.
 [http://dx.doi.org/10.1139/bcb-2019-0031] [PMID:  31199889]

[119]
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.
 [http://dx.doi.org/10.1016/j.bbrc.2018.09.069] [PMID:  30241943]

[120]
Shen L, Hu Y, Lou J, 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.
 [http://dx.doi.org/10.3892/mmr.2019.10011] [PMID:  30864721]

[121]
Kong P, Yu Y, Wang L, et al. circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells. Nucleic Acids Res  2019; 47(7): 3580-93.
 [http://dx.doi.org/10.1093/nar/gkz141] [PMID:  30820544]

[122]
He Q, Shao D, Hao S, et al. CircSCAP aggravates oxidized low-density lipoprotein-induced macrophage injury by upregulating PDE3B by miR-221-5p in atherosclerosis. J Cardiovasc Pharmacol  2021; 78(5): e749-60.
 [http://dx.doi.org/10.1097/FJC.0000000000001118] [PMID:  34321402]

[123]
Wang X, Bai M. CircTM7SF3 contributes to oxidized low-density lipoprotein-induced apoptosis, inflammation and oxidative stress through targeting miR-206/ASPH axis in atherosclerosis cell model in vitro. BMC Cardiovasc Disord  2021; 21(1): 51.
 [http://dx.doi.org/10.1186/s12872-020-01800-x] [PMID:  33526034]

[124]
Peng W, Li S, Chen S, Yang J, Sun Z. Hsa_circ_0003204 knockdown weakens Ox-LDL-induced cell injury by regulating miR-188-3p/TRPC6 axis in human carotid artery endothelial cells and THP-1 cells. Front Cardiovasc Med  2021; 8731890
 [http://dx.doi.org/10.3389/fcvm.2021.731890] [PMID:  34912856]

[125]
Ma J, Liu J, Li T, Ren J. Hsa_circ_0030042 facilitates the proliferation and migration of vascular smooth muscle cells via the miR-514a-3p/FOXO1 axis. J Endovasc Ther  2022; 29(4): 611-22.
 [http://dx.doi.org/10.1177/15266028211057086] [PMID:  35382622]
Cite As
Current Vascular Pharmacology

The Emerging Role of CircRNAs in Atherosclerosis

Abstract

Graphical Abstract
