Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Alterations in the vascular smooth muscle cells (VSMC) phenotype play a critical role in the pathogenesis of several cardiovascular diseases, including hypertension, atherosclerosis, and restenosis after angioplasty. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (approximately 19–25 nucleotides in length) that function as regulators in various physiological and pathophysiological events. Recent studies have suggested that aberrant miRNAs’ expression might underlie VSMC phenotypic transformation, appearing to regulate the phenotypic transformations of VSMCs by targeting specific genes that either participate in the maintenance of the contractile phenotype or contribute to the transformation to alternate phenotypes, and affecting atherosclerosis, hypertension, and coronary artery disease by altering VSMC proliferation, migration, differentiation, inflammation, calcification, oxidative stress, and apoptosis, suggesting an important regulatory role in vascular remodeling for maintaining vascular homeostasis. This review outlines recent progress in the discovery of miRNAs and elucidation of their mechanisms of action and functions in VSMC phenotypic regulation. Importantly, as the literature supports roles for miRNAs in modulating vascular remodeling and for maintaining vascular homeostasis, this area of research will likely provide new insights into clinical diagnosis and prognosis and ultimately facilitate the identification of novel therapeutic targets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of data and materials

Not applicable.

Code availability

Not applicable.

Abbreviations

VSMC:

Vascular smooth muscle cells

CVD:

Cardiovascular diseases

ncRNA:

Non-coding RNA

miRNA:

MicroRNAs

lncRNAs:

Long non-coding RNAs

circRNAs:

Circular RNAs

PTEN:

Phosphatase and tensin homologue

Bcl-2:

B-cell lymphoma 2

KLF4:

Kruppel-like factor 4

BMP-4:

Bone morphogenic protein-4

PDCD4:

Programmed cell death protein 4

DOCK:

Dedicator of cytokinesis

VEGF:

Vascular endothelial-derived growth factor

PDGF:

Platelet-derived growth factor

TRIB3:

Tribbles homologue-3

RhoA:

Ras homologue family member A

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-related kinase

PCNA:

Proliferating cell nuclear antigen

LATS2:

Large tumor suppressor 2

CREG:

Cellular repressor of E1A-stimulated genes

TRB3:

Tribbles homologue 3

Sp-1:

Specificity protein-1

ELK1:

ETS transcription factor ELK1

ACE:

Angiotensin-converting enzyme

MYL9:

Myosin light chain 9

MMP-9:

Matrix metallopeptidase 9

STIM1:

Stromal interaction molecule 1

NOR1:

Orphan nuclear receptor

SCF:

Stem cell factor

PAH:

Pulmonary arterial hypertension

HPASMC:

Human pulmonary arterial smooth muscle cells

FoxO4:

Forkhead box O4

FGF9:

Fibroblast growth factor 9

MYADM:

Myeloid-associated differentiation

ECM:

Extracellular matrix

EVI1:

Eosinophil integration site 1 protein homologue

HASMC:

Human arterial smooth-muscle cells

STAT5A:

Signal transducer and activator of transcription 5A

ITGB1:

Integrin beta 1

Myh11:

Myosin heavy chain 11

T2DM:

Type 2 diabetes mellitus

Emp2:

Epithelial membrane protein 2

Cav1:

Caveolin-1

Grb10:

Growth factor receptor-bound protein 10

EGR2:

Early growth response 2

MST2:

Mammalian sterile 20-like kinase 2

MOAP1:

Modulator of apoptosis 1

AAA:

Abdominal aortic aneurysm

HAOSMC:

Human aortic smooth muscle cells

P4HA1:

Prolyl 4-hydroxylase subunit alpha 1

PVAT:

Perivascular adipose tissue

EVs:

Extracellular vesicles

EC:

Endothelial cell

VCAM-1:

Vascular cell adhesion molecule 1

NF-κB:

NF-kappa B

RCN2:

Reticulocalbin-2

STAT3:

Signal transducer and activator of transcription 3

DNMT3A:

DNA methyltransferases 3A

SMA:

Smooth Muscle α-actin

SM22α:

Smooth muscle22alpha

SM-MHC:

Smooth muscle-myosin heavy chain

References

  1. Gibbons GH, Dzau VJ (1994) The emerging concept of vascular remodeling. N Engl J Med 330:1431–1438

    CAS  PubMed  Google Scholar 

  2. Basatemur GL, Jørgensen HF, Clarke MCH et al (2019) Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol 16:727–744

    PubMed  Google Scholar 

  3. Green ID, Liu R, Wong JJL (2021) The expanding role of alternative splicing in vascular smooth muscle cell plasticity. Int J Mol Sci 22:10213

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Miano JM, Fisher EA, Majesky MW (2021) Fate and state of vascular smooth muscle cells in atherosclerosis. Circulation 143:2110–2116

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Grootaert MOJ, Moulis M, Roth L et al (2018) Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis. Cardiovasc Res 114:622–634

    CAS  PubMed  Google Scholar 

  6. Oller J, Gabandé-Rodríguez E, Ruiz-Rodríguez MJ et al (2021) Extracellular tuning of mitochondrial respiration leads to aortic aneurysm. Circulation 143:2091–2109

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Bonetti J, Corti A, Lerouge L et al (2021) Phenotypic modulation of macrophages and vascular smooth muscle cells in atherosclerosis-nitro-redox interconnections. Antioxidants (Basel, Switzerland) 10:516

    CAS  PubMed  Google Scholar 

  8. Chen Y, Su X, Qin Q et al (2020) New insights into phenotypic switching of VSMCs induced by hyperhomocysteinemia: role of endothelin-1 signaling. Biomed Pharmacother 123:109758

    CAS  PubMed  Google Scholar 

  9. Durham AL, Speer MY, Scatena M et al (2018) Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. Cardiovasc Res 114:590–600

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Sorokin V, Vickneson K, Kofidis T et al (2020) Role of vascular smooth muscle cell plasticity and interactions in vessel wall inflammation. Front Immunol 11:599415

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gabbiani G, Schmid E, Winter S et al (1981) Vascular smooth muscle cells differ from other smooth muscle cells: predominance of vimentin filaments and a specific alpha-type actin. Proc Natl Acad Sci USA 78:298–302

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Babij P, Kelly C, Periasamy M (1991) Characterization of a mammalian smooth muscle myosin heavy-chain gene: complete nucleotide and protein coding sequence and analysis of the 5’ end of the gene. Proc Natl Acad Sci USA 88:10676–10680

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826

    CAS  PubMed  Google Scholar 

  14. Ambros V, Lee RC, Lavanway A et al (2003) MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr Biol 13:807–818

    CAS  PubMed  Google Scholar 

  15. Saliminejad K, Khorram Khorshid HR, Soleymani Fard S, Ghaffari SH (2019) An overview of microRNAs: biology, functions, therapeutics, and analysis methods. J Cell Physiol 234:5451–5465

    CAS  PubMed  Google Scholar 

  16. Galagali H, Kim JK (2020) The multifaceted roles of microRNAs in differentiation. Curr Opin Cell Biol 67:118–140

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Agbu P, Carthew RW (2021) MicroRNA-mediated regulation of glucose and lipid metabolism. Nat Rev Mol Cell Biol 22:425–438

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhu J, Liu B, Wang Z et al (2019) Exosomes from nicotine-stimulated macrophages accelerate atherosclerosis through miR-21-3p/PTEN-mediated VSMC migration and proliferation. Theranostics 9:6901–6919

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Zeng Z, Xia L, Fan X et al (2019) Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair. J Clin Invest 129:1372–1386

    PubMed  PubMed Central  Google Scholar 

  20. Xu F, Zhong J-Y, Lin X et al (2020) Melatonin alleviates vascular calcification and ageing through exosomal miR-204/miR-211 cluster in a paracrine manner. J Pineal Res 68:e12631

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kong P, Yu Y, Wang L et al (2019) 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 47:3580–3593

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang Y, Wang Y, Zhang L et al (2020) Reduced platelet miR-223 induction in kawasaki disease leads to severe coronary artery pathology through a miR-223/PDGFRβ vascular smooth muscle cell axis. Circ Res 127:855–873

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang G-S, Zheng B, Qin Y et al (2020) derived miRNAs suppress vascular remodeling through regulating OTUD7B/KLF4/NMHC IIA axis. Theranostics 10:7787–7811

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ji R, Cheng Y, Yue J et al (2007) MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 100:1579–1588

    CAS  PubMed  Google Scholar 

  25. Scortegagna M, Lau E, Zhang T et al (2015) PDK1 and SGK3 contribute to the growth of BRAF-mutant melanomas and are potential therapeutic targets. Cancer Res 75:1399–1412

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Maegdefessel L, Azuma J, Toh R et al (2012) MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med. 4:122ra22

    PubMed  PubMed Central  Google Scholar 

  27. Jin H, Li DY, Chernogubova E et al (2018) Local delivery of miR-21 stabilizes fibrous caps in vulnerable atherosclerotic lesions. Mol Ther 26:1040–1055

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Ajuyah P, Hill M, Ahadi A et al (2019) MicroRNA (miRNA)-to-miRNA regulation of programmed cell death 4 (PDCD4). Mol Cell Biol 39:e00086-e119

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim K, Kim S, Moh SH, Kang H (2015) Kaempferol inhibits vascular smooth muscle cell migration by modulating BMP-mediated miR-21 expression. Mol Cell Biochem 407:143–149

    CAS  PubMed  Google Scholar 

  30. Kang H, Davis-Dusenbery BN, Nguyen PH et al (2012) Bone morphogenetic protein 4 promotes vascular smooth muscle contractility by activating microRNA-21 (miR-21), which down-regulates expression of family of dedicator of cytokinesis (DOCK) proteins. J Biol Chem 287:3976–3986

    CAS  PubMed  Google Scholar 

  31. Cordes KR, Sheehy NT, White MP et al (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460:705–710

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Davis BN, Hilyard AC, Nguyen PH et al (2009) Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem 284:3728–3738

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu X, Cheng Y, Zhang S et al (2009) A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res 104:476–487

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Albinsson S, Suarez Y, Skoura A et al (2010) MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function. Arterioscler Thromb Vasc Biol 30:1118–1126

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Nie X, Wang Q, Jiao K (2011) Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis. Mech Dev 128:200–207

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Sequeira-Lopez MLS, Weatherford ET, Borges GR et al (2010) The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 21:460–467

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Tang Y, Yu S, Liu Y et al (2017) MicroRNA-124 controls human vascular smooth muscle cell phenotypic switch via Sp1. Am J Physiol Heart Circ Physiol 313:H641–H649

    PubMed  Google Scholar 

  38. Boon RA, Seeger T, Heydt S et al (2011) MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 109:1115–1119

    CAS  PubMed  Google Scholar 

  39. Zheng B, Zheng C-Y, Zhang Y et al (2018) Regulatory crosstalk between KLF5, miR-29a and Fbw7/CDC4 cooperatively promotes atherosclerotic development. Biochim Biophys Acta Mol Basis Dis 1864:374–386

    CAS  PubMed  Google Scholar 

  40. Merk DR, Chin JT, Dake BA et al (2012) miR-29b participates in early aneurysm development in Marfan syndrome. Circ Res 110:312–324

    CAS  PubMed  Google Scholar 

  41. Yang P, Wu P, Liu X et al (2020) MiR-26b suppresses the development of Stanford type A aortic dissection by regulating HMGA2 and TGF-β/Smad3 signaling pathway. Ann Thorac Cardiovasc Surg 26:140–150

    PubMed  Google Scholar 

  42. Shan F, Li J, Huang Q-Y (2014) HIF-1 alpha-induced up-regulation of miR-9 contributes to phenotypic modulation in pulmonary artery smooth muscle cells during hypoxia. J Cell Physiol 229:1511–1520

    CAS  PubMed  Google Scholar 

  43. Chen W-J, Chen Y-H, Hsu Y-J et al (2018) MicroRNA-132 targeting PTEN contributes to cilostazol-promoted vascular smooth muscle cell differentiation. Atherosclerosis 274:1–7

    CAS  PubMed  Google Scholar 

  44. Xu J, Li L, Yun H, Han Y (2015) MiR-138 promotes smooth muscle cells proliferation and migration in db/db mice through down-regulation of SIRT1. Biochem Biophys Res Commun 463:1159–1164

    CAS  PubMed  Google Scholar 

  45. Sun S, Zheng B, Han M et al (2011) miR-146a and Krüppel-like factor 4 form a feedback loop to participate in vascular smooth muscle cell proliferation. EMBO Rep 12:56–62

    CAS  PubMed  Google Scholar 

  46. Afzal TA, Luong LA, Chen D et al (2016) NCK Associated protein 1 modulated by miRNA-214 determines vascular smooth muscle cell migration, proliferation, and neointima hyperplasia. J Am Heart Assoc 5:e004629

    PubMed  PubMed Central  Google Scholar 

  47. Seong M, Kang H (2020) Hypoxia-induced miR-1260b regulates vascular smooth muscle cell proliferation by targeting GDF11. BMB Rep 53:206–211

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Choi S, Park M, Kim J et al (2018) TNF-α elicits phenotypic and functional alterations of vascular smooth muscle cells by miR-155-5p-dependent down-regulation of cGMP-dependent kinase 1. J Biol Chem 293:14812–14822

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Lu X, Yin D, Zhou B, Li T (2018) MiR-135a promotes inflammatory responses of vascular smooth muscle cells from db/db mice via downregulation of FOXO1. Int Heart J 59:170–179

    CAS  PubMed  Google Scholar 

  50. Gabunia K, Herman AB, Ray M et al (2017) Induction of MiR133a expression by IL-19 targets LDLRAP1 and reduces oxLDL uptake in VSMC. J Mol Cell Cardiol 105:38–48

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Lai Z, Lin P, Weng X et al (2018) MicroRNA-574-5p promotes cell growth of vascular smooth muscle cells in the progression of coronary artery disease. Biomed Pharmacother 97:162–167

    CAS  PubMed  Google Scholar 

  52. Yang K, Ren J, Li X et al (2020) Prevention of aortic dissection and aneurysm via an ALDH2-mediated switch in vascular smooth muscle cell phenotype. Eur Heart J 41:2442–2453

    CAS  PubMed  Google Scholar 

  53. Farina FM, Hall GF, Serio S, Zani S, Climent M, Salvarani N, Carullo P, Civilini E, Condorelli G, Leonardo Elia MQ, Expand A (2020) Correction to: miR-128-3p Is a novel regulator of vascular smooth muscle cell phenotypic switch and vascular diseases. Circ Res 127:e141

    Google Scholar 

  54. Gao X-F, Wang Z-M, Chen A-Q et al (2021) Plasma small extracellular vesicle-carried miRNA-501-5p promotes vascular smooth muscle cell phenotypic modulation-mediated in-stent restenosis. Oxid Med Cell Longev 2021:6644970

    PubMed  PubMed Central  Google Scholar 

  55. Li Y, Li H, Xing W et al (2021) Vascular smooth muscle cell-specific miRNA-214 knockout inhibits angiotensin II-induced hypertension through upregulation of Smad7. FASEB J 35:e21947

    CAS  PubMed  Google Scholar 

  56. Li R, Jiang Q, Zheng Y (2021) Circ_0002984 induces proliferation, migration and inflammation response of VSMCs induced by ox-LDL through miR-326-3p/VAMP3 axis in atherosclerosis. J Cell Mol Med 25:8028–8038

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Grootaert MOJ, Finigan A, Figg NL et al (2021) SIRT6 protects smooth muscle cells from senescence and reduces atherosclerosis. Circ Res 128:474–491

    CAS  PubMed  Google Scholar 

  58. Ouyang S, You J, Zhi C et al (2021) Ferroptosis: the potential value target in atherosclerosis. Cell Death Dis 12:782

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Pi S, Mao L, Chen J et al (2021) The P2RY12 receptor promotes VSMC-derived foam cell formation by inhibiting autophagy in advanced atherosclerosis. Autophagy 17:980–1000

    CAS  PubMed  Google Scholar 

  60. Chan MC, Hilyard AC, Wu C et al (2010) Molecular basis for antagonism between PDGF and the TGFbeta family of signalling pathways by control of miR-24 expression. EMBO J 29:559–573

    CAS  PubMed  Google Scholar 

  61. Talasila A, Yu H, Ackers-Johnson M et al (2013) Myocardin regulates vascular response to injury through miR-24/-29a and platelet-derived growth factor receptor-β. Arterioscler Thromb Vasc Biol 33:2355–2365

    CAS  PubMed  Google Scholar 

  62. Yang X, Dong M, Wen H et al (2017) MiR-26a contributes to the PDGF-BB-induced phenotypic switch of vascular smooth muscle cells by suppressing Smad1. Oncotarget 8:75844–75853

    PubMed  PubMed Central  Google Scholar 

  63. Liu X, Cheng Y, Chen X et al (2011) MicroRNA-31 regulated by the extracellular regulated kinase is involved in vascular smooth muscle cell growth via large tumor suppressor homolog 2. J Biol Chem 286:42371–42380

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang J, Yan C-H, Li Y et al (2013) MicroRNA-31 controls phenotypic modulation of human vascular smooth muscle cells by regulating its target gene cellular repressor of E1A-stimulated genes. Exp Cell Res 319:1165–1175

    CAS  PubMed  Google Scholar 

  65. Kim S, Hata A, Kang H (2014) Down-regulation of miR-96 by bone morphogenetic protein signaling is critical for vascular smooth muscle cell phenotype modulation. J Cell Biochem 115:889–895

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Dong S, Xiong W, Yuan J et al (2013) MiRNA-146a regulates the maturation and differentiation of vascular smooth muscle cells by targeting NF-κB expression. Mol Med Rep 8:407–412

    PubMed  Google Scholar 

  67. Sahoo S, Meijles DN, Al Ghouleh I et al (2016) MEF2C-MYOCD and Leiomodin1 suppression by miRNA-214 promotes smooth muscle cell phenotype switching in pulmonary arterial hypertension. PLoS ONE 11:e0153780

    PubMed  PubMed Central  Google Scholar 

  68. Lu X, Ma S-T, Zhou B, Lı T (2019) MiR-9 promotes the phenotypic switch of vascular smooth muscle cells by targeting KLF5. Turkish J Med Sci 49:928–938

    CAS  Google Scholar 

  69. Ma Q, Zhang J, Zhang M et al (2020) MicroRNA-29b targeting of cell division cycle 7-related protein kinase (CDC7) regulated vascular smooth muscle cell (VSMC) proliferation and migration. Ann Transl Med 8:1496

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Yang C, Xiao X, Huang L et al (2021) Role of Kruppel-like factor 4 in atherosclerosis. Clin Chim Acta 512:135–141

    CAS  PubMed  Google Scholar 

  71. Ghaleb AM, Yang VW (2017) Krüppel-like factor 4 (KLF4): what we currently know. Gene 611:27–37

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Cao B-J, Wang X-W, Zhu L et al (2019) MicroRNA-146a sponge therapy suppresses neointimal formation in rat vein grafts. IUBMB Life 71:125–133

    CAS  PubMed  Google Scholar 

  73. Zheng B, Bernier M, Zhang X et al (2015) miR-200c-SUMOylated KLF4 feedback loop acts as a switch in transcriptional programs that control VSMC proliferation. J Mol Cell Cardiol 82:201–212

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Arevalo-Martinez M, Cidad P, Moreno-Estar S et al (2021) miR-126 contributes to the epigenetic signature of diabetic vascular smooth muscle and enhances antirestenosis effects of Kv1.3 blockers. Mol. Metab. 53:101306

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Chen J, Yin H, Jiang Y et al (2011) Induction of microRNA-1 by myocardin in smooth muscle cells inhibits cell proliferation. Arterioscler Thromb Vasc Biol 31:368–375

    CAS  PubMed  Google Scholar 

  76. Torella D, Iaconetti C, Catalucci D et al (2011) MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ Res 109:880–893

    CAS  PubMed  Google Scholar 

  77. Lovren F, Pan Y, Quan A et al (2012) MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 126:S81–S90

    CAS  PubMed  Google Scholar 

  78. Shyu K-G, Cheng W-P, Wang B-W (2015) Angiotensin II downregulates MicroRNA-145 to regulate Kruppel-like factor 4 and myocardin expression in human coronary arterial smooth muscle cells under high glucose conditions. Mol Med 21:616–625

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Cheng Y, Liu X, Yang J et al (2009) MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res 105:158–166

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhang Y-N, Xie B-D, Sun L et al (2016) Phenotypic switching of vascular smooth muscle cells in the “normal region” of aorta from atherosclerosis patients is regulated by miR-145. J Cell Mol Med 20:1049–1061

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Ohnaka M, Marui A, Yamahara K et al (2014) Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype. J Thorac Cardiovasc Surg 148:676–682

    CAS  PubMed  Google Scholar 

  82. Nishio H, Minatoya K, Masumoto H (2020) A rabbit venous interposition model mimicking revascularization surgery using vein grafts to assess intimal hyperplasia under arterial blood pressure. J Vis Exp 15:e60931

    Google Scholar 

  83. Chin DD, Poon C, Wang J et al (2021) miR-145 micelles mitigate atherosclerosis by modulating vascular smooth muscle cell phenotype. Biomaterials 273:120810

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Nishio H, Masumoto H, Sakamoto K et al (2019) MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model. J Thorac Cardiovasc Surg 157:2242–2251

    CAS  PubMed  Google Scholar 

  85. Chen M, Zhang Y, Li W, Yang J (2018) MicroRNA-145 alleviates high glucose-induced proliferation and migration of vascular smooth muscle cells through targeting ROCK1. Biomed Pharmacother 99:81–86

    CAS  PubMed  Google Scholar 

  86. Li Y, Huang J, Jiang Z et al (2016) MicroRNA-145 regulates platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration by targeting CD40. Am J Transl Res 8:1813–1825

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Boucher JM, Peterson SM, Urs S et al (2011) The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells. J Biol Chem 286:28312–28321

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Kim S, Kang H (2013) miR-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation. BMB Rep 46:550–554

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Xu F, Ahmed ASI, Kang X et al (2015) MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP. Arterioscler Thromb Vasc Biol 35:2145–2152

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Li P, Zhu N, Yi B et al (2013) MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and vascular neointimal formation. Circ Res 113:1117–1127

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Merlet E, Atassi F, Motiani RK et al (2013) miR-424/322 regulates vascular smooth muscle cell phenotype and neointimal formation in the rat. Cardiovasc Res 98:458–468

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Li P, Liu Y, Yi B et al (2013) MicroRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1. Cardiovasc Res 99:185–193

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Choe N, Kwon J-S, Kim YS et al (2015) The microRNA miR-34c inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia by targeting stem cell factor. Cell Signal 27:1056–1065

    CAS  PubMed  Google Scholar 

  94. Jalali S, Ramanathan GK, Parthasarathy PT et al (2012) Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation. PLoS ONE 7:e46808

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Li H, Xiang Y, Fan L-J et al (2017) Myocardin inhibited the gap protein connexin 43 via promoted miR-206 to regulate vascular smooth muscle cell phenotypic switch. Gene 616:22–30

    CAS  PubMed  Google Scholar 

  96. Iaconetti C, De Rosa S, Polimeni A et al (2015) Down-regulation of miR-23b induces phenotypic switching of vascular smooth muscle cells in vitro and in vivo. Cardiovasc Res 107:522–533

    CAS  PubMed  Google Scholar 

  97. Au Yeung CL, Tsang TY, Yau PL, Kwok TT (2011) Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway. Oncogene 30:2401–2410

    CAS  PubMed  Google Scholar 

  98. Liu H, Hao W, Wang X, Su H (2016) miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells. J Toxicol Sci 41:185–193

    CAS  PubMed  Google Scholar 

  99. Dong N, Wang W, Tian J et al (2017) MicroRNA-182 prevents vascular smooth muscle cell dedifferentiation via FGF9/PDGFRβ signaling. Int J Mol Med 39:791–798

    PubMed  PubMed Central  Google Scholar 

  100. Sun L, Bai Y, Zhao R et al (2016) Oncological miR-182-3p, a novel smooth muscle cell phenotype modulator, evidences from model rats and patients. Arterioscler Thromb Vasc Biol 36:1386–1397

    CAS  PubMed  Google Scholar 

  101. Bai Y, Wang J, Chen Y et al (2021) The miR-182/Myadm axis regulates hypoxia-induced pulmonary hypertension by balancing the BMP- and TGF-β-signalling pathways in an SMC/EC-crosstalk-associated manner. Basic Res Cardiol 116:53

    PubMed  Google Scholar 

  102. Liao J, Zhang Y, Wu Y et al (2018) Akt modulation by miR-145 during exercise-induced VSMC phenotypic switching in hypertension. Life Sci 199:71–79

    CAS  PubMed  Google Scholar 

  103. Humphrey JD, Schwartz MA (2021) Vascular mechanobiology: homeostasis, adaptation, and disease. Annu Rev Biomed Eng 23:1–27

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Peng Y, Wu S, Li Y, Crane JL (2020) Type H blood vessels in bone modeling and remodeling. Theranostics 10:426–436

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Brown IAM, Diederich L, Good ME et al (2018) Vascular smooth muscle remodeling in conductive and resistance arteries in hypertension. Arterioscler Thromb Vasc Biol 38:1969–1985

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Humbert M, Guignabert C, Bonnet S et al (2019) Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J 53:1801887

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Yang F, Chen Q, He S et al (2018) miR-22 is a novel mediator of vascular smooth muscle cell phenotypic modulation and neointima formation. Circulation 137:1824–1841

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Han Y, Zhang J, Huang S et al (2021) MicroRNA-223-3p inhibits vascular calcification and the osteogenic switch of vascular smooth muscle cells. J Biol Chem 296:100483

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Wang J, Hu X, Hu X et al (2021) MicroRNA-520c-3p targeting of RelA/p65 suppresses atherosclerotic plaque formation. Int J Biochem Cell Biol 131:105873

    CAS  PubMed  Google Scholar 

  110. Chen Q, Yang F, Guo M et al (2015) miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration. J Mol Cell Cardiol 89:75–86

    CAS  PubMed  Google Scholar 

  111. Wang Y, Dong C-Q, Peng G-Y et al (2019) MicroRNA-134-5p regulates media degeneration through inhibiting VSMC phenotypic switch and migration in thoracic aortic dissection. Mol Ther Nucleic Acids 16:284–294

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Farina FM, Hall IF, Serio S et al (2020) miR-128-3p is a novel regulator of vascular smooth muscle cell phenotypic switch and vascular diseases. Circ Res 126:e120–e135

    CAS  PubMed  Google Scholar 

  113. Elia L, Kunderfranco P, Carullo P et al (2018) UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease. J Clin Invest 128:2473–2486

    PubMed  PubMed Central  Google Scholar 

  114. Zhang M, Li F, Wang X et al (2020) MiR-145 alleviates Hcy-induced VSMC proliferation, migration, and phenotypic switch through repression of the PI3K/Akt/mTOR pathway. Histochem Cell Biol 153:357–366

    CAS  PubMed  Google Scholar 

  115. McCallinhart PE, Cho Y, Sun Z et al (2020) Reduced stiffness and augmented traction force in type 2 diabetic coronary microvascular smooth muscle. Am J Physiol Heart Circ Physiol 318:H1410–H1419

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Torella D, Iaconetti C, Tarallo R et al (2018) miRNA regulation of the hyperproliferative phenotype of vascular smooth muscle cells in diabetes. Diabetes 67:2554–2568

    PubMed  Google Scholar 

  117. Reddy MA, Das S, Zhuo C et al (2016) Regulation of vascular smooth muscle cell dysfunction under diabetic conditions by miR-504. Arterioscler Thromb Vasc Biol 36:864–873

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Yang Z, Zheng B, Zhang Y et al (2015) miR-155-dependent regulation of mammalian sterile 20-like kinase 2 (MST2) coordinates inflammation, oxidative stress and proliferation in vascular smooth muscle cells. Biochim Biophys Acta 1852:1477–1489

    CAS  PubMed  Google Scholar 

  119. Zhang B, Zhang G, Wei T et al (2019) MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis. Oxid Med Cell Longev 2019:2691514

    PubMed  PubMed Central  Google Scholar 

  120. Peng J, He X, Zhang L, Liu P (2018) MicroRNA-26a protects vascular smooth muscle cells against H2O2-induced injury through activation of the PTEN/AKT/mTOR pathway. Int J Mol Med 42:1367–1378

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Watterston C, Zeng L, Onabadejo A, Childs SJ (2019) MicroRNA26 attenuates vascular smooth muscle maturation via endothelial BMP signalling. PLoS Genet 15:e1008163

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Radi R (2018) Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine. Proc Natl Acad Sci USA 115:5839–5848

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Farzaei MH, Zobeiri M, Parvizi F et al (2018) Curcumin in liver diseases: a systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients 10:855

    PubMed  PubMed Central  Google Scholar 

  124. Sivandzade F, Prasad S, Bhalerao A, Cucullo L (2019) NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches. Redox Biol 21:101059

    CAS  PubMed  Google Scholar 

  125. Zhang Q, Liu J, Duan H et al (2021) Activation of Nrf2/HO-1 signaling: an important molecular mechanism of herbal medicine in the treatment of atherosclerosis the protection of vascular endothelial cells from oxidative stress. J Adv Res 34:43–63

    CAS  PubMed  PubMed Central  Google Scholar 

  126. van der Pol A, van Gilst WH, Voors AA, van der Meer P (2019) Treating oxidative stress in heart failure: past, present and future. Eur J Heart Fail 21:425–435

    PubMed  Google Scholar 

  127. Ornatowski W, Lu Q, Yegambaram M et al (2020) Complex interplay between autophagy and oxidative stress in the development of pulmonary disease. Redox Biol 36:101679

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Ebrahimi SO, Reiisi S, Shareef S (2020) miRNAs, oxidative stress, and cancer: a comprehensive and updated review. J Cell Physiol 235:8812–8825

    CAS  PubMed  Google Scholar 

  129. Petrie JR, Guzik TJ, Touyz RM (2018) Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol 34:575–584

    PubMed  Google Scholar 

  130. Chang M, Liu G, Wang Y et al (2022) Long non-coding RNA LINC00299 knockdown inhibits ox-LDL-induced T/G HA-VSMC injury by regulating miR-135a-5p/XBP1 axis in atherosclerosis. Panminerva Med 64:38–47

    PubMed  Google Scholar 

  131. Liu Y, Zhong Z, Xiao L et al (2021) Identification of Circ-FNDC3B, an overexpressed circRNA in abdominal aortic aneurysm, as a regulator of vascular smooth muscle cells. Int Heart J 62:1387–1398

    CAS  PubMed  Google Scholar 

  132. Zhang J, Cai W, Fan Z et al (2019) MicroRNA-24 inhibits the oxidative stress induced by vascular injury by activating the Nrf2/Ho-1 signaling pathway. Atherosclerosis 290:9–18

    CAS  PubMed  Google Scholar 

  133. Chistiakov DA, Sobenin IA, Orekhov AN, Bobryshev YV (2015) Human miR-221/222 in physiological and atherosclerotic vascular remodeling. Biomed Res Int 2015:354517

    PubMed  PubMed Central  Google Scholar 

  134. Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123:4195–4200

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Clause KC, Barker TH (2013) Extracellular matrix signaling in morphogenesis and repair. Curr Opin Biotechnol 24:830–833

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Wang X, Hu G, Zhou J (2010) Repression of versican expression by microRNA-143. J Biol Chem 285:23241–23250

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Shi X, Ma W, Pan Y et al (2020) MiR-126-5p promotes contractile switching of aortic smooth muscle cells by targeting VEPH1 and alleviates Ang II-induced abdominal aortic aneurysm in mice. Lab Invest 100:1564–1574

    CAS  PubMed  Google Scholar 

  138. Sorushanova A, Delgado LM, Wu Z et al (2019) The collagen suprafamily: from biosynthesis to advanced biomaterial development. Adv Mater 31:e1801651

    PubMed  Google Scholar 

  139. Zhang C, Chen D, Maguire EM et al (2018) Cbx3 inhibits vascular smooth muscle cell proliferation, migration, and neointima formation. Cardiovasc Res 114:443–455

    CAS  PubMed  Google Scholar 

  140. Chen W, Yu F, Di M et al (2018) MicroRNA-124-3p inhibits collagen synthesis in atherosclerotic plaques by targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) in vascular smooth muscle cells. Atherosclerosis 277:98–107

    CAS  PubMed  Google Scholar 

  141. Bekelis K, Kerley-Hamilton JS, Teegarden A et al (2016) MicroRNA and gene expression changes in unruptured human cerebral aneurysms. J Neurosurg 125:1390–1399

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107

    CAS  PubMed  Google Scholar 

  143. Xu S, Ilyas I, Little PJ et al (2021) Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacol Rev 73:924–967

    CAS  PubMed  Google Scholar 

  144. Poznyak A, Grechko AV, Poggio P et al (2020) The diabetes mellitus-atherosclerosis connection: the role of lipid and glucose metabolism and chronic inflammation. Int J Mol Sci 21:1835

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Fodor A, Lazar AL, Buchman C et al (2021) MicroRNAs: the link between the metabolic syndrome and oncogenesis. Int J Mol Sci 22:6337

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Brennan E, Wang B, McClelland A et al (2017) Protective effect of let-7 miRNA family in regulating inflammation in diabetes-associated atherosclerosis. Diabetes 66:2266–2277

    CAS  PubMed  Google Scholar 

  147. Li X, Ballantyne LL, Yu Y, Funk CD (2019) Perivascular adipose tissue-derived extracellular vesicle miR-221-3p mediates vascular remodeling. FASEB J 33:12704–12722

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Harris TA, Yamakuchi M, Ferlito M et al (2008) MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 105:1516–1521

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Yang D, Sun C, Zhang J et al (2018) Proliferation of vascular smooth muscle cells under inflammation is regulated by NF-κB p65/microRNA-17/RB pathway activation. Int J Mol Med 41:43–50

    CAS  PubMed  Google Scholar 

  150. Liao X-B, Zhang Z-Y, Yuan K et al (2013) MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells. Endocrinology 154:3344–3352

    CAS  PubMed  Google Scholar 

  151. Zhao J, Liu Z, Chang Z (2021) Osteogenic differentiation and calcification of human aortic smooth muscle cells is induced by the RCN2/STAT3/miR-155-5p feedback loop. Vascul Pharmacol 136:106821

    CAS  PubMed  Google Scholar 

  152. Choe N, Shin S, Joung H et al (2020) The microRNA miR-134-5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells. J Cell Mol Med 24:10542–10550

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Mackenzie NCW, Staines KA, Zhu D et al (2014) miRNA-221 and miRNA-222 synergistically function to promote vascular calcification. Cell Biochem Funct 32:209–216

    CAS  PubMed  Google Scholar 

  154. Gui T, Zhou G, Sun Y et al (2012) MicroRNAs that target Ca(2+) transporters are involved in vascular smooth muscle cell calcification. Lab Invest 92:1250–1259

    CAS  PubMed  Google Scholar 

  155. Sudo R, Sato F, Azechi T, Wachi H (2015) MiR-29-mediated elastin down-regulation contributes to inorganic phosphorus-induced osteoblastic differentiation in vascular smooth muscle cells. Genes Cells 20:1077–1087

    CAS  PubMed  Google Scholar 

  156. Cui R-R, Li S-J, Liu L-J et al (2012) MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res 96:320–329

    CAS  PubMed  Google Scholar 

  157. Wen P, Cao H, Fang L et al (2014) miR-125b/Ets1 axis regulates transdifferentiation and calcification of vascular smooth muscle cells in a high-phosphate environment. Exp Cell Res 322:302–312

    CAS  PubMed  Google Scholar 

  158. Xia Z-Y, Hu Y, Xie P-L et al (2015) Runx2/miR-3960/miR-2861 positive feedback loop is responsible for osteogenic transdifferentiation of vascular smooth muscle cells. Biomed Res Int 2015:624037

    PubMed  PubMed Central  Google Scholar 

  159. Hao J, Zhang L, Cong G et al (2016) MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell calcification via a SATB2/Runx2 pathway. Cell Tissue Res 366:733–746

    CAS  PubMed  Google Scholar 

  160. Liu J, Xiao X, Shen Y et al (2017) MicroRNA-32 promotes calcification in vascular smooth muscle cells: implications as a novel marker for coronary artery calcification. PLoS ONE 12:e0174138

    PubMed  PubMed Central  Google Scholar 

  161. Pan W, Liang J, Tang H et al (2020) Differentially expressed microRNA profiles in exosomes from vascular smooth muscle cells associated with coronary artery calcification. Int J Biochem Cell Biol 118:105645

    CAS  PubMed  Google Scholar 

  162. Kapustin AN, Shanahan CM (2016) Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. J Physiol 594:2905–2914

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Guo Y, Bao S, Guo W et al (2019) Bone marrow mesenchymal stem cell-derived exosomes alleviate high phosphorus-induced vascular smooth muscle cells calcification by modifying microRNA profiles. Funct Integr Genomics 19:633–643

    CAS  PubMed  Google Scholar 

  164. Feng S, Gao L, Zhang D et al (2019) MiR-93 regulates vascular smooth muscle cell proliferation, and neointimal formation through targeting Mfn2. Int J Biol Sci 15:2615–2626

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Park N, Kang H (2020) BMP-induced MicroRNA-101 expression regulates vascular smooth muscle cell migration. Int J Mol Sci 21:4764

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Kim GR, Zhao T, Kee HJ et al (2021) MicroRNA-212-5p and its target PAFAH1B2 suppress vascular proliferation and contraction via the downregulation of RhoA. PLoS ONE 16:e0249146

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Wang X, Li H, Zhang Y et al (2021) Suppression of miR-4463 promotes phenotypic switching in VSMCs treated with Ox-LDL. Cell Tissue Res 383:1155–1165

    CAS  PubMed  Google Scholar 

  168. Zhou B, Wu L-L, Zheng F et al (2021) miR-31-5p promotes oxidative stress and vascular smooth muscle cell migration in spontaneously hypertensive rats via inhibiting FNDC5 expression. Biomedicines 9:1009

    PubMed  PubMed Central  Google Scholar 

  169. Wang L, Wang Z, Zhang R et al (2021) MiR-4787-5p regulates vascular smooth muscle cell apoptosis by targeting PKD1 and inhibiting the PI3K/Akt/FKHR pathway. J Cardiovasc Pharmacol 78:288–296

    CAS  PubMed  Google Scholar 

  170. Han Z-L, Wang H-Q, Zhang T-S et al (2020) Up-regulation of exosomal miR-106a may play a significant role in abdominal aortic aneurysm by inducing vascular smooth muscle cell apoptosis and targeting TIMP-2, an inhibitor of metallopeptidases that suppresses extracellular matrix degradation. Eur Rev Med Pharmacol Sci 24:8087–8095

    PubMed  Google Scholar 

  171. Qin Y, Zheng B, Yang G-S et al (2020) Tanshinone IIA inhibits VSMC inflammation and proliferation in vivo and in vitro by downregulating miR-712-5p expression. Eur J Pharmacol 880:173140

    CAS  PubMed  Google Scholar 

  172. Yang B, Gao X, Sun Y et al (2020) Dihydroartemisinin alleviates high glucose-induced vascular smooth muscle cells proliferation and inflammation by depressing the miR-376b-3p/KLF15 pathway. Biochem Biophys Res Commun 530:574–580

    CAS  PubMed  Google Scholar 

  173. Chong H, Wei Z, Na M et al (2020) The PGC-1α/NRF1/miR-378a axis protects vascular smooth muscle cells from FFA-induced proliferation, migration and inflammation in atherosclerosis. Atherosclerosis 297:136–145

    CAS  PubMed  Google Scholar 

  174. Lin X, Xu F, Cui R-R et al (2018) Arterial calcification is regulated via an miR-204/DNMT3a regulatory circuit both in vitro and in female mice. Endocrinology 159:2905–2916

    CAS  PubMed  Google Scholar 

  175. He X, Lian Z, Yang Y et al (2020) Long Non-coding RNA PEBP1P2 suppresses proliferative VSMCs phenotypic switching and proliferation in atherosclerosis. Mol Ther Nucleic Acids 22:84–98

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Dong K, Shen J, He X et al (2021) CARMN is an evolutionarily conserved smooth muscle cell-specific LncRNA that maintains contractile phenotype by binding myocardin. Circulation 144:1856–1875

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Yu J, Wang W, Yang J et al (2022) LncRNA PSR regulates vascular remodeling through encoding a novel protein arteridin. Circ Res 131:768–787

    CAS  PubMed  Google Scholar 

  178. Zhao J, Zhang W, Lin M et al (2016) MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program. Arterioscler Thromb Vasc Biol 36:2088–2099

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Jin L, Lin X, Yang L et al (2018) AK098656, a novel vascular smooth muscle cell-dominant long noncoding RNA, promotes hypertension. Hypertens (Dallas, Tex. 1979) 71:262–272

    CAS  Google Scholar 

  180. Fang G, Qi J, Huang L, Zhao X (2019) LncRNA MRAK048635_P1 is critical for vascular smooth muscle cell function and phenotypic switching in essential hypertension. Biosci Rep 39:BSR20182229

  181. Ahmed ASI, Dong K, Liu J et al (2018) Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. Proc Natl Acad Sci USA 115:E8660–E8667

    PubMed  PubMed Central  Google Scholar 

  182. Lim Y-H, Ryu J, Kook H, Kim Y-K (2020) Identification of long noncoding RNAs involved in differentiation and survival of vascular smooth muscle cells. Mol Ther Nucleic Acids 22:209–221

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Song Y, Wang T, Mu C et al (2022) 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 32:1560–1570

    CAS  PubMed  Google Scholar 

  184. Mao Y-Y, Wang J-Q, Guo X-X et al (2018) Circ-SATB2 upregulates STIM1 expression and regulates vascular smooth muscle cell proliferation and differentiation through miR-939. Biochem Biophys Res Commun 505:119–125

    CAS  PubMed  Google Scholar 

  185. Liu Y, Huang Y, Zhang X et al (2022) CircZXDC promotes vascular smooth muscle cell transdifferentiation via regulating miRNA-125a-3p/ABCC6 in moyamoya disease. Cells 11:3792

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Ye M, Ni Q, Wang H et al (2023) CircRNA circCOL1A1 Acts as a sponge of miR-30a-5p to promote vascular smooth cell phenotype switch through regulation of smad1 expression. Thromb Haemost 123:097–107

    Google Scholar 

  187. Ji X, Takahashi R, Hiura Y et al (2009) Plasma miR-208 as a biomarker of myocardial injury. Clin Chem 55:1944–1949

    CAS  PubMed  Google Scholar 

  188. Olivieri F, Antonicelli R, Lorenzi M et al (2013) Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol 167:531–536

    PubMed  Google Scholar 

  189. Cheng Y, Tan N, Yang J et al (2010) A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci (Lond) 119:87–95

    CAS  PubMed  Google Scholar 

  190. Widera C, Gupta SK, Lorenzen JM et al (2011) Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. J Mol Cell Cardiol 51:872–875

    CAS  PubMed  Google Scholar 

  191. Grabmaier U, Clauss S, Gross L et al (2017) Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction—the SITAGRAMI-miR analysis. Int J Cardiol 244:30–36

    CAS  PubMed  Google Scholar 

  192. Goren Y, Kushnir M, Zafrir B et al (2012) Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 14:147–154

    CAS  PubMed  Google Scholar 

  193. Täubel J, Hauke W, Rump S et al (2021) Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study. Eur Heart J 42:178–188

    PubMed  Google Scholar 

  194. Schwartz Longacre L, Kloner RA, Arai AE et al (2011) New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop. Circulation 124:1172–1179

    PubMed  Google Scholar 

  195. Kiechl S, Lorenz E, Reindl M et al (2002) Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 347:185–192

    CAS  PubMed  Google Scholar 

  196. Schulte C, Molz S, Appelbaum S et al (2015) miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease. PLoS ONE 10:e0145930

    PubMed  PubMed Central  Google Scholar 

  197. Che H-L, Bae I-H, Lim KS et al (2016) Novel fabrication of MicroRNA nanoparticle-coated coronary stent for prevention of post-angioplasty restenosis. Korean Circ J 46:23–32

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Wang D, Deuse T, Stubbendorff M et al (2015) Local MicroRNA modulation using a novel Anti-miR-21-eluting stent effectively prevents experimental in-stent restenosis. Arterioscler Thromb Vasc Biol 35:1945–1953

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Alshanwani AR, Riches-Suman K, O’Regan DJ et al (2018) MicroRNA-21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells. IUBMB Life 70:649–657

    CAS  PubMed  Google Scholar 

  200. Li Y, Yan L, Zhang W et al (2014) MicroRNA-21 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting activator protein-1. Am J Transl Res 6:507–516

    PubMed  PubMed Central  Google Scholar 

  201. Stein JJ, Iwuchukwu C, Maier KG, Gahtan V (2014) Thrombospondin-1-induced vascular smooth muscle cell migration and proliferation are functionally dependent on microRNA-21. Surgery 155:228–233

    PubMed  Google Scholar 

  202. Wang M, Li W, Chang G-Q et al (2011) MicroRNA-21 regulates vascular smooth muscle cell function via targeting tropomyosin 1 in arteriosclerosis obliterans of lower extremities. Arterioscler Thromb Vasc Biol 31:2044–2053

    CAS  PubMed  Google Scholar 

  203. Michel J-B, Jondeau G, Milewicz DM (2018) From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta. Cardiovasc Res 114:578–589

    CAS  PubMed  PubMed Central  Google Scholar 

  204. Méndez-Barbero N, Gutiérrez-Muñoz C, Blanco-Colio LM (2021) Cellular crosstalk between endothelial and smooth muscle cells in vascular wall remodeling. Int J Mol Sci 22:7284

    PubMed  PubMed Central  Google Scholar 

  205. Wadey K, Lopes J, Bendeck M, George S (2018) Role of smooth muscle cells in coronary artery bypass grafting failure. Cardiovasc Res 114:601–610

    CAS  PubMed  PubMed Central  Google Scholar 

  206. Hergenreider E, Heydt S, Tréguer K et al (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14:249–256

    CAS  PubMed  Google Scholar 

  207. Li B, Fan J, Chen N (2018) A novel regulator of type II diabetes: MicroRNA-143. Trends Endocrinol Metab 29:380–388

    CAS  PubMed  Google Scholar 

  208. Vacante F, Denby L, Sluimer JC, Baker AH (2019) The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease. Vascul Pharmacol 112:24–30

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Coleman CB, Lightell DJ, Moss SC et al (2013) Elevation of miR-221 and -222 in the internal mammary arteries of diabetic subjects and normalization with metformin. Mol Cell Endocrinol 374:125–129

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Michael A. Hill (Dalton Cardiovascular Research Center, University of Missouri-Columbia) for technical assistance with professional English language editing of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China [Grant no. 81800434], and Grant of Sichuan Province Science and Technology Agency Grant [2022YFS0627].

Author information

Author notes

  1. Gang Wang and Yulin Luo have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Longmatan District, No. 1, Section 1, Xianglin Road, Luzhou, Sichuan, China

    Gang Wang, Xiaojun Gao, Jianbo Wu, Dan Fang & Mao Luo

  2. Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, the School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China

    Gang Wang, Xiaojun Gao, Jianbo Wu, Dan Fang & Mao Luo

  3. School of Pharmacy, Chongqing Medical University, Chongqing, China

    Gang Wang & Feifei Yang

  4. GCP Center, Affiliated Hospital (Traditional Chinese Medicine) of Southwest Medical University, Luzhou, China

    Yulin Luo

  5. Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, Sichuan, China

    Yu Liang & Mao Luo

Authors
  1. Gang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yulin Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaojun Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feifei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianbo Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dan Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mao Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GW, YL, DF, and ML conceived the idea, analysis of literature, and writing of the manuscript; GW and FY read the literature and revised the article; XG, YL, and JW read through and corrected the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Dan Fang or Mao Luo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest regarding the publication of this article.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Luo, Y., Gao, X. et al. MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling. Cell. Mol. Life Sci. 80, 144 (2023). https://doi.org/10.1007/s00018-023-04793-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00018-023-04793-w

Keywords

Search

Navigation