The role of noncoding RNA in aortic dissection

Abstract

Aortic dissection (AD) is a rapidly progressive cardiovascular disease associated with high mortality. The core pathogenic mechanisms of AD include apoptosis and phenotypic switching of vascular smooth muscle cells (VSMCs), remodeling and degradation of the extracellular matrix (ECM), and vascular inflammation. However, the detailed molecular mechanisms remain incompletely understood. Noncoding RNAs (ncRNAs) are RNA molecules that do not encode proteins. Recent studies have confirmed that ncRNAs with aberrant expression exert critical regulatory functions in the pathogenesis and progression of AD, and several ncRNAs have shown significant application potential in the early diagnosis, conservative treatment, and prognostic assessment of AD. This review summarizes the latest research progress on the regulatory mechanisms of various ncRNAs in AD, and critically evaluates their potential clinical utility as clinical biomarkers and therapeutic targets for AD.

Keywords

Aortic dissection / vascular smooth muscle / extracellular matrix / inflammation / noncoding RNA

References

[1] Isselbacher EM, Preventza O, Hamilton Black J 3rd, et al.; Peer Review Committee Members. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines Circulation 2022 146 e334 482

[2] Erbel R,Aboyans V,Boileau C.et al. ; Grupa Robocza Europejskiego Towarzystwa Kardiologicznego (ESC) do spraw rozpoznawania i leczenia chorób aorty. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases Kardiol Pol 2014 72 1169 252

[3] Rensen SS,Doevendans PA,van Eys GJ. Regulation and characteristics of vascular smooth muscle cell phenotypic diversity Neth Heart J 2007 15 100 8 PMC1847757

[4] Ikonomidis JS,Jones JA,Barbour JR.et al. Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome Circulation 2006 114 I365 70

[5] He R,Guo DC,Estrera AL.et al. Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections J Thorac Cardiovasc Surg 2006 131 671 8

[6] The Writing Committee of the Report on Cardiovascular Health and Diseases in China. Report on cardiovascular health and diseases in China 2021: an updated summary Biomed Environ Sci 2022 35 573 603

[7] Fattori R,Cao P,De Rango P.et al. Interdisciplinary expert consensus document on management of type B aortic dissection J Am Coll Cardiol 2013 61 1661 78

[8] Hagan PG,Nienaber CA,Isselbacher EM.et al. The international registry of acute aortic dissection (IRAD): new insights into an old disease JAMA 2000 283 897 903

[9] Estrera AL, Miller CC 3rd, Safi HJ, et al. Outcomes of medical management of acute type B aortic dissection Circulation 2006 114 I384 9

[10] Evangelista A,Isselbacher EM,Bossone E.et al. ; IRAD Investigators. Insights from the international registry of acute aortic dissection: a 20-year experience of collaborative clinical research Circulation 2018 137 1846 60

[11] Esteller M. Non-coding RNAs in human disease Nat Rev Genet 2011 12 861 74

[12] Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function Cell 2004 116 281 97

[13] Rinn JL,Chang HY. Genome regulation by long noncoding RNAs Annu Rev Biochem 2012 81 145 66 PMC3858397

[14] Memczak S,Jens M,Elefsinioti A.et al. Circular RNAs are a large class of animal RNAs with regulatory potency Nature 2013 495 333 8

[15] Elia L,Quintavalle M,Zhang J.et al. The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human disease Cell Death Differ 2009 16 1590 8 PMC3014107

[16] Ding W,Liu Y,Su Z,Li Q,Wang J,Gao Y. Emerging role of non-coding RNAs in aortic dissection Biomolecules 2022 12 1336 PMC9599213

[17] Wang XJ,Huang B,Zhang L.et al. Differential gene expression in aortic tissues between patients with acute aortic dissection and normal controls Chin J Mol Cardiol 2014 14 812-5. (in Chinese).

[18] Guo DC,Regalado ES,Minn C.et al. Familial thoracic aortic aneurysms and dissections: identification of a novel locus for stable aneurysms with a low risk for progression to aortic dissection Circ Cardiovasc Genet 2011 4 36 42 PMC3739448

[19] Huang W,Huang C,Ding H.et al. Involvement of miR-145 in the development of aortic dissection via inducing proliferation, migration, and apoptosis of vascular smooth muscle cells J Clin Lab Anal 2020 34 e23028

[20] Xiao Y,Sun Y,Ma X.et al. MicroRNA-22 inhibits the apoptosis of vascular smooth muscle cell by targeting p38MAPKα in vascular remodeling of aortic dissection Mol Ther Nucleic Acids 2020 22 1051 62 PMC7691156

[21] Zou S. Analysis of microRNA expression and regulatory mechanisms in Stanford type A aortic dissection. Dissertation, University of South China, Hunan, 2015. (in Chinese). Available from: https://med.wanfangdata.com.cn/Paper/Detail?dbid=WF_XW&id=DegreePaper_D774884. [Last accessed on 2 June 2026]

[22] Wang Z,Zhuang X,Chen B,Feng D,Li G,Wei M. The role of miR-107 as a potential biomarker and cellular factor for acute aortic dissection DNA Cell Biol 2020 39 1895 906

[23] Tang Y,Yu S,Liu Y,Zhang J,Han L,Xu Z. MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1 Am J Physiol Heart Circ Physiol 2017 313 H641 9

[24] Wang Y,Dong CQ,Peng GY.et al. MicroRNA-134-5p regulates media degeneration through inhibiting VSMC phenotypic switch and migration in thoracic aortic dissection Mol Ther Nucleic Acids 2019 16 284 94 PMC6446055

[25] Shao Y. The role of miR200c-3p in regulating endothelial cell apoptosis and proliferation and vascular smooth muscle cell phenotypic switching in aortic dissection. Dissertation, Chongqing Medical University, Chongqing, 2022. (in Chinese)

[26] Ren M,Wang T,Wei X.et al. LncRNA H19 regulates smooth muscle cell functions and participates in the development of aortic dissection through sponging miR-193b-3p Biosci Rep 2021 41 PMC7823186

[27] Song Y,Wang T,Mu C,Gui W,Deng Y,Ma R. LncRNA SENCR overexpression attenuated the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection via the miR-206/myocardin axis Nutr Metab Cardiovasc Dis 2022 32 1560 70

[28] Zhang K,Qi Y,Wang M,Chen Q. Long non-coding RNA HIF1A-AS2 modulates the proliferation, migration, and phenotypic switch of aortic smooth muscle cells in aortic dissection via sponging microRNA-33b Bioengineered 2022 13 6383 95 PMC8974049

[29] Li S,Zhao X,Cheng S,Li J,Bai X,Meng X. Downregulating long non-coding RNA PVT1 expression inhibited the viability, migration and phenotypic switch of PDGF-BB-treated human aortic smooth muscle cells via targeting miR-27b-3p Hum Cell 2021 34 335 48

[30] Zhao X,Cheng S,Li S,Li J,Bai X,Xi J. CDKN2B-AS1 aggravates the pathogenesis of human thoracic aortic dissection by sponge to miR-320d J Cardiovasc Pharmacol 2020 76 592 601

[31] Lai Y,Li J,Zhong L.et al. The pseudogene PTENP1 regulates smooth muscle cells as a competing endogenous RNA Clin Sci 2019 133 1439 55

[32] Zhang X,Wu H,Mai C,Qi Y. Long noncoding RNA XIST/miR-17/PTEN axis modulates the proliferation and apoptosis of vascular smooth muscle cells to affect stanford type a aortic dissection J Cardiovasc Pharmacol 2020 76 53 62

[33] Wang W,Liu Q,Wang Y.et al. LINC01278 sponges miR-500b-5p to regulate the expression of ACTG2 to control phenotypic switching in human vascular smooth muscle cells during aortic dissection J Am Heart Assoc 2021 10 e018062

[34] Lin Y,Huang H,Yu Y.et al. Long non-coding RNA RP11-465L10.10 promotes vascular smooth muscle cells phenotype switching and MMP9 expression via the NF-κB pathway Ann Transl Med 2021 9 1776 PMC8756256

[35] Liu Y,Wang L,Lei D.et al. Circ_0000006 and circ_0000160 regulate hsa-let-7e-5p/UBQLN4 axis in aortic dissection progression PLoS One 2024 19 e0304668 PMC11142605

[36] Huang MX,Piao HL,Wang Y.et al. Circ_0022920 maintains the contractile phenotype of human aortic vascular smooth muscle cells via sponging microRNA-650 and promoting transforming growth factor beta receptor 1 expression in angiotensin II-induced models for aortic dissection J Am Heart Assoc 2023 12 e027425

[37] Cao X,Fang H,Zhou L. CircNRIP1 promotes proliferation, migration and phenotypic switch of Ang II-induced HA-VSMCs by increasing CXCL5 mRNA stability via recruiting IGF2BP1 Autoimmunity 2024 57 2304820

[38] Xu Z,Zhong K,Guo G.et al. circ_TGFBR2 inhibits vascular smooth muscle cells phenotypic switch and suppresses aortic dissection progression by sponging miR-29a J Inflamm Res 2021 14 5877 90 PMC8593842

[39] Li M,Li G,Yang Y.et al. piRNA-823 is a novel potential therapeutic target in aortic dissection Pharmacol Res 2023 196 106932

[40] Xu J,Shi GP. Vascular wall extracellular matrix proteins and vascular diseases Biochim Biophys Acta 2014 1842 2106 19 PMC4188798

[41] Tian T,Luo F,Zhao LP.et al. Research progress on the role and mechanism of extracellular matrix in aortic aneurysm and aortic dissection Chin J Clin Thorac Cardiovasc Surg 2024 31 1376-84. (in Chinese).

[42] Sun YY. The role and mechanism of NANOG transcriptional regulation of miR-20a in promoting extracellular matrix degradation in the pathogenesis of thoracic aortic dissection. Dissertation, Naval Medical University, Shanghai, 2022.(in Chinese)

[43] Wei Y,Yuan M,Wei M.et al. Study on the role and mechanism of microRNA-183 in extracellular matrix remodeling of acute aortic dissection Chin J Mod Med 2022 32 28 32

[44] Sun J,Chen G,Jing Y.et al. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing Cell Physiol Biochem 2018 46 1027 41

[45] Zhang S,Zhao S,Han X.et al. Lnc-C2orf63-4-1 confers VSMC homeostasis and prevents aortic dissection formation via STAT3 interaction Front Cell Dev Biol 2021 9 792051 PMC8685433

[46] Zou M,Huang C,Li X.et al. Circular RNA expression profile and potential function of hsa_circRNA_101238 in human thoracic aortic dissection Oncotarget 2017 8 81825 37 PMC5669851

[47] Liu DB,He YF,Chen GJ.et al. Construction of a circRNA-Mediated ceRNA network reveals novel biomarkers for aortic dissection Int J Gen Med 2022 15 3951 64 PMC9013255

[48] Liu X,Chen W,Zhu G.et al. Single-cell RNA sequencing identifies an Il1rn⁺/Trem1⁺ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection Cell Discov 2022 8 11 PMC8821555

[49] Guo LL,Wu MT,Zhang LW.et al. Blocking interleukin-1 beta reduces the evolution of thoracic aortic dissection in a rodent model Eur J Vasc Endovasc Surg 2020 60 916 24

[50] Wu YW,Hu B,Guo XD,Fu Q,Zou ZJ. Effect of microRNA-30a regulation of mitogen-activated protein kinase pathway on aortic coarctation in rats. Acta Anat Sin 2024;55:222-8. (in Chinese).

[51] Daniel F,Kalies K,Hehl L.et al. MicroRNA-127-3p regulates inflammatory response in injury-induced vascular remodeling and cellular senescence in vascular smooth muscle cells through mTor Cardiovasc Res 2024 120 cvae088.006

[52] Wang P. The mechanism of Lnc-OIP5-AS1 competitively binding to miR-143-3p in the pathogenesis of aortic dissection. Dissertation, Wuhan University, Wuhan, 2021. (in Chinese)

[53] Wang K. Circular RNA hsa_circ_0079929 promotes endothelial inflammation in aortic dissection by activating PDE4D. Dissertation, Qingdao University, Shandong, 2023. (in Chinese)

[54] Liang Q,Zhou Z,Li H.et al. Identification of pathological-related and diagnostic potential circular RNAs in Stanford type A aortic dissection Front Cardiovasc Med 2022 9 1074835 PMC9880160

[55] Pape LA,Awais M,Woznicki EM.et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the international registry of acute aortic dissection J Am Coll Cardiol 2015 66 350 8

[56] Barile L,Vassalli G. Exosomes: therapy delivery tools and biomarkers of diseases Pharmacol Ther 2017 174 63 78

[57] Liao M,Zou S,Weng J.et al. A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis J Vasc Surg 2011 53 1341 1349.e3

[58] Boon RA,Seeger T,Heydt S.et al. MicroRNA-29 in aortic dilation: implications for aneurysm formation Circ Res 2011 109 1115 9

[59] Xu Z,Wang Q,Pan J.et al. Characterization of serum miRNAs as molecular biomarkers for acute Stanford type A aortic dissection diagnosis Sci Rep 2017 7 13659 PMC5651857

[60] Chai T,Yang X,Zhuang X.et al. Upregulation of miR-222-3p alleviates the symptom of aortic dissection through targeting STAT3 Life Sci 2022 310 121051

[61] Zhang D,Zhao X,Wang B,Liu X,Aizezi A,Ma X. Circulating exosomal miRNAs as novel biomarkers for acute aortic dissection: a diagnostic accuracy study Medicine 2023 102 e34474 PMC10378726

[62] Chen H,Li Y,Li Z,Shi Y,Zhu H. Diagnostic biomarkers and aortic dissection: a systematic review and meta-analysis BMC Cardiovasc Disord 2023 23 497 PMC10563263

[63] Michalik KM,You X,Manavski Y.et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth Circ Res 2014 114 1389 97

[64] Rodor J,Klimi E,Brown SD.et al. Functional screening identifies miRNAs with a novel function inhibiting vascular smooth muscle cell proliferation Mol Ther 2025 33 615 30 PMC11852670

[65] Li Y,Maegdefessel L. Non-coding RNA contribution to thoracic and abdominal aortic aneurysm disease development and progression Front Physiol 2017 8 429 PMC5472729

[66] He X,Wang S,Li M.et al. Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis Theranostics 2019 9 5558 76 PMC6735383

[67] Tamblin-Hopper P,Kiss-Toth E,Sudbery I.et al. The potential therapeutic applications of long non-coding RNAs J Transl Genet Genom 2024 8 225 43

[68] He X,Li X,Han Y.et al. CircRNA Chordc1 protects mice from abdominal aortic aneurysm by contributing to the phenotype and growth of vascular smooth muscle cells Mol Ther Nucleic Acids 2022 27 81 98 PMC8649900

[69] Dogra S,Kouznetsova VL,Kesari S,Tsigelny IF. Development of a miRNA-based deep learning model for autism spectrum disorder diagnosis Adv Technol Neurosci 2025 2 72 6

[70] Zhang RL,Wang WM,Li JQ.et al. The role of miR-155 in cardiovascular diseases: potential diagnostic and therapeutic targets Int J Cardiol Cardiovasc Risk Prev 2025 24 200355 PMC11699627

[71] D’Alessandra Y,Valerio V,Moschetta D.et al. Extraction-free absolute quantification of circulating miRNAs by chip-based digital PCR Biomedicines 2022 10 1354 PMC9220272

[72] Ferracin M,Negrini M. Quantification of circulating microRNAs by droplet digital PCR. In: Karlin-neumann G, Bizouarn F, editors. Digital PCR. New York: Springer; 2018. pp. 445-57

[73] Wang L,Zhang S,Xu Z,Zhang J,Li L,Zhao G. The diagnostic value of microRNA-4787-5p and microRNA-4306 in patients with acute aortic dissection Am J Transl Res 2017 9 5138 49

[74] Dong J,Bao J,Feng R.et al. Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection Sci Rep 2017 7 12784 PMC5630636

[75] Wang W,Liu C,He D.et al. CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway Pharmacol Res 2024 204 107189