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Aging and disease    2020, Vol. 11 Issue (1) : 164-178     DOI: 10.14336/AD.2019.0402
Review Article |
Roles and Functions of Exosomal Non-coding RNAs in Vascular Aging
Yu-Qing Ni, Xiao Lin, Jun-Kun Zhan, You-Shuo Liu*
Department of Geriatrics, Institute of Aging and Geriatrics, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
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Aging is a progressive loss of physiological integrity and functionality process which increases susceptibility and mortality to diseases. Vascular aging is a specific type of organic aging. The structure and function changes of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cause of vascular aging, which could influence the threshold, process, and severity of vascular related diseases. Accumulating evidences demonstrate that exosomes serve as novel intercellular information communicator between cell to cell by delivering variety biologically active cargos, especially exosomal non-coding RNAs (ncRNAs), which are associated with most of aging-related biological and functional disorders. In this review, we will summerize the emerging roles and mechanisms of exosomal ncRNAs in vascular aging and vascular aging related diseases, focusing on the role of exosomal miRNAs and lncRNAs in regulating the functions of ECs and VSMCs. Moreover, the relationship between the ECs and VSMCs linked by exosomes, the potential diagnostic and therapeutic application of exosomes in vascular aging and the clinical evaluation and treatment of vascular aging and vascular aging related diseases will also be discussed.

Keywords exosomes      endothelial cells      vascular smooth muscle cells      vascular aging      vascular diseases     
Corresponding Authors: You-Shuo Liu   
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These authors contributed equally to this work.

Just Accepted Date: 08 April 2019   Issue Date: 15 January 2020
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Yu-Qing Ni
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Yu-Qing Ni,Xiao Lin,Jun-Kun Zhan, et al. Roles and Functions of Exosomal Non-coding RNAs in Vascular Aging[J]. Aging and disease, 2020, 11(1): 164-178.
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Exosomal non-coding RNAsCargosTargetsECs functionsReference
Exosomal miRNAsmiR-122-5pHGFpro-proliferation, pro-migration[23]
miR-210-3pHGFpro-proliferation, pro-migration[23]
miR-296-5pHGFpro-proliferation, pro-migration[23]
miR-376c-3pHGFpro-proliferation, pro-migration[23]
miR-214ATMpro-proliferation, anti-senescence, pro-angiogenesis[24]
pro-proliferation, pro-migration,
[25] [35]
miR-19ANGPT1pro-proliferation, pro-migration[25]
miR-20aANGPT1pro-proliferation, pro-migration[25]
miR-30cANGPT1pro-proliferation, pro-migration[25]
miR-126ANGPT1pro-proliferation, pro-migration[25]
miR-92aSOCS5anti- proliferation, pro-inflammation[26] [30]
miR-21RhoBanti- proliferation, pro-inflammation[27] [31]
miR-24Sp1anti- proliferation[28]
miR-15aVEGF, NF-kBpro-inflammation[32, 33]
miR-27aVEGF, EGFRpro-inflammation[32, 33]
miR-34aBCL2, SIRT1pro-inflammation[32, 33]
miR-106b-5pANG2anti- angiogenesis[38]
miR-320IGF-1, Hsp20, Ets2anti- angiogenesis[39]
Exosomal lncRNAsHOTTIPcyclin D1, PCNApro-proliferation, pro-migration[48]
POU3F3bFGF, VEGFpro-proliferation, pro-migration,
MALAT1IL-6, TNF-α, SAA3anti- proliferation, pro-migration,
[59, 60]
CCAT2TGFβ, Bcl-2pro-angiogenesis, anti-apoptosis[55]
Meg3Unknownanti- angiogenesis[57]
GAS5P53, Caspase 3, Caspase 7pro-apoptosis[58]
Table 1  Exosomal non-coding RNAs implicated in ECs functions.
Exosomal non-coding RNAsCargosTargetsECs functionsReference
Exosomal miRNAsmiR-31MAPK/ERK, LATS2promote phenotype transition[63]
miR-133Sp1promote phenotype transition[64]
miR-223MEF2C, RhoBpromote phenotype transition[65]
miR-26aSmad1inhibit phenotype transition[66]
miR-130aBMP2, TGFβ1pro-proliferation[68]
miR-221/222p27, p57pro-proliferation[69, 70]
miR-143-3pTGFβpro-migration, pro-angiogenesis[79]
miR-125bEts1, Osterixanti-transdifferentiation,
[84, 85]
miR-126-3pVEGF, ANG1, ANG2, MMP9, TSP1pro-angiogenesis[86]
miR-92aMKK4anti-apoptosis, anti-senescence[88]
Exosomal lncRNAsMALAT1Unknownpro-proliferation, pro-migration[92]
MEG3p53anti-proliferation, anti-migration[93]
lncRNA-p21p53anti-proliferation, pro-apoptosis[94]
HOTAIRALPL, BMP2anti-calcification[95]
Table 2  Exosomal non-coding RNAs implicated in VSMCs functions.
Figure 1.  The communication between ECs and VSMCs via exosomal ncRNAs. The blue and brown arrows indicate that exosomal miR206 and miR-143/145 secreted by ECs regulate the functions of VSMCs. The green and purple arrows indicate that exosomal miR-155 and miR-143 secreted by VSMCs regulate the functions of ECs.
Heart DiseasesmiR-221/222CADPromote the progression of CAD[103]
miR-208aCADPromote the progression of CAD[104]
miR-126CADInhibit the progression of CAD[105]
miR-17-92CADInhibit the progression of CAD[106]
miR-22AMIProtect against CMCs apoptosis[108]
miR-133AMIPromote the progression of AMI[109]
miR-21AMI, HFPromote CMCs loss[110, 113]
miR-24HFPromote the progression of HF[114]
miR-214HFPromote the progression of HF[115]
HypertensionmiR-211EHActivate the axis of RAAS[119]
miR-615EHActivate the axis of RAAS[119]
miR-155EHRegulate the progression of VC[99]
Cerebrovascular DiseasesmiR-126AISInhibit microglial activation and inflammatory response[122]
miR-30d-5pAISInhibit autophagy-mediated microglial polarization to M1[123]
miR-181b-5pAISpromoted BMEC angiogenesis[37]
miR-146aVCIDInhibit inflammatory effects on damaged astrocytes[124]
Kidney DiseasesmiR-200bCKDRegulate the progression of renal fibrosis[126]
miR-16CKDRegulate the progression of CKD[127]
PADmiR-92aHind Limb IschemiaInhibit functional recovery[129]
Table 3  Roles of exosomal miRNAs in vascular aging related diseases.
[1] Wu M, Rementer C, Giachelli CM (2013). Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int, 93: 365-73.
[2] Lin X, Zhan JK, Wang YJ, Tan P, Chen YY, Deng HQ, et al. (2016). Function, Role, and Clinical Application of MicroRNAs in Vascular Aging. Biomed Res Int, 2016: 6021394.
[3] Jenjaroenpun P, Kremenska Y, Nair VM, Kremenskoy M, Joseph B, Kurochkin IV (2013). Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing. PeerJ, 1: e201.
[4] Lai RC, Chen TS, Lim SK (2011). Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med, 6: 481-92.
[5] Liao XB, Zhang ZY, Yuan K, Liu Y, Feng X, Cui RR, et al. (2013). MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells. Endocrinology, 154: 3344-52.
[6] Cui RR, Li SJ, Liu LJ, Yi L, Liang QH, Zhu X, et al. (2012). MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res, 96: 320-9.
[7] Liu FJ, Wen T, Liu L (2012). MicroRNAs as a novel cellular senescence regulator. Ageing Res Rev, 11: 41-50.
[8] Dimmeler S, Nicotera P (2013). MicroRNAs in age-related diseases. EMBO Mol Med, 5: 180-90.
[9] Kapustin AN, Shanahan CM (2016). Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. J Physiol, 594: 2905-14.
[10] Zhang C, Zhang K, Huang F, Feng W, Chen J, Zhang H, et al. (2018). Exosomes, the message transporters in vascular calcification. J Cell Mol Med, 22: 4024-4033.
[11] Yan B, Wang Z (2012). Long noncoding RNA: its physiological and pathological roles. DNA Cell Biol, 31 Suppl 1: S34-41.
[12] Gupta SK, Piccoli MT, Thum T (2014). Non-coding RNAs in cardiovascular ageing. Ageing Res Rev, 17: 79-85.
[13] Maiese K (2017). Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease. Curr Neurovasc Res, 14: 82-88.
[14] He C, Zheng S, Luo Y, Wang B (2018). Exosome Theranostics: Biology and Translational Medicine. Theranostics, 8: 237-255.
[15] O'Loughlin AJ, Woffindale CA, Wood MJ (2012). Exosomes and the emerging field of exosome-based gene therapy. Curr Gene Ther, 12: 262-74.
[16] Tabas I, Garcia-Cardena G, Owens GK (2015). Recent insights into the cellular biology of atherosclerosis. J Cell Biol, 209: 13-22.
[17] Gimbrone MAJr, Garcia-Cardena G (2016). Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res, 118: 620-36.
[18] Staszel T, Zapala B, Polus A, Sadakierska-Chudy A, Kiec-Wilk B, Stepien E, et al. (2011). Role of microRNAs in endothelial cell pathophysiology. Pol Arch Med Wewn, 121: 361-6.
[19] Das S, Halushka MK (2015). Extracellular vesicle microRNA transfer in cardiovascular disease. Cardiovasc Pathol, 24: 199-206.
[20] Kishore R, Garikipati VN, Gumpert A (2016). Tiny Shuttles for Information Transfer: Exosomes in Cardiac Health and Disease. J Cardiovasc Transl Res, 9: 169-75.
[21] Santulli G (2016). MicroRNAs and Endothelial (Dys) Function. J Cell Physiol, 231: 1638-44.
[22] Araldi E, Suarez Y (2016). MicroRNAs as regulators of endothelial cell functions in cardiometabolic diseases. Biochim Biophys Acta, 1861: 2094-2103.
[23] Jia L, Zhou X, Huang X, Xu X, Jia Y, Wu Y, et al. (2018). Maternal and umbilical cord serum-derived exosomes enhance endothelial cell proliferation and migration. Faseb j, 32: 4534-4543.
[24] van Balkom BW, de Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM, et al. (2013). Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood, 121: 3997-4006, s1-15.
[25] Garcia NA, Ontoria-Oviedo I, Gonzalez-King H, Diez-Juan A, Sepulveda P (2015). Glucose Starvation in Cardiomyocytes Enhances Exosome Secretion and Promotes Angiogenesis in Endothelial Cells. PLoS One, 10: e0138849.
[26] Iaconetti C, Polimeni A, Sorrentino S, Sabatino J, Pironti G, Esposito G, et al. (2012). Inhibition of miR-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury. Basic Res Cardiol, 107: 296.
[27] Jin C, Zhao Y, Yu L, Xu S, Fu G (2013). MicroRNA-21 mediates the rapamycin-induced suppression of endothelial proliferation and migration. FEBS Lett, 587: 378-85.
[28] Svensson D, Gidlof O, Turczynska KM, Erlinge D, Albinsson S, Nilsson BO (2014). Inhibition of microRNA-125a promotes human endothelial cell proliferation and viability through an antiapoptotic mechanism. J Vasc Res, 51: 239-45.
[29] Qin G, Dong Z, Zeng P, Liu M, Liao X (2013). Association of vitamin D receptor BsmI gene polymorphism with risk of osteoporosis: a meta-analysis of 41 studies. Mol Biol Rep, 40: 497-506.
[30] Loyer X, Potteaux S, Vion AC, Guerin CL, Boulkroun S, Rautou PE, et al. (2014). Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res, 114: 434-43.
[31] Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ, et al. (2011). MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci U S A, 108: 10355-60.
[32] Goodwin AJ, Guo C, Cook JA, Wolf B, Halushka PV, Fan H (2015). Plasma levels of microRNA are altered with the development of shock in human sepsis: an observational study. Crit Care, 19: 440.
[33] Real JM, Ferreira LRP, Esteves GH, Koyama FC, Dias MVS, Bezerra-Neto JE, et al. (2018). Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis? Crit Care, 22: 68.
[34] Li J, Tan M, Xiang Q, Zhou Z, Yan H (2017). Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response. Thromb Res, 154: 96-105.
[35] Lee C, Mitsialis SA, Aslam M, Vitali SH, Vergadi E, Konstantinou G, et al. (2012). Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation, 126: 2601-11.
[36] Liang X, Zhang L, Wang S, Han Q, Zhao RC (2016). Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. J Cell Sci, 129: 2182-9.
[37] Yang Y, Cai Y, Zhang Y, Liu J, Xu Z (2018). Exosomes Secreted by Adipose-Derived Stem Cells Contribute to Angiogenesis of Brain Microvascular Endothelial Cells Following Oxygen-Glucose Deprivation In Vitro Through MicroRNA-181b/TRPM7 Axis. J Mol Neurosci, 65: 74-83.
[38] Li Y, Liang J, Hu J, Ren X, Sheng Y (2018). Down-regulation of exosomal miR-106b-5p derived from cholesteatoma perimatrix fibroblasts promotes angiogenesis in endothelial cells by overexpression of Angiopoietin 2. Cell Biol Int, 42: 1300-1310.
[39] Wang X, Huang W, Liu G, Cai W, Millard RW, Wang Y, et al. (2014). Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol, 74: 139-50.
[40] Chen Y, Li D, Xu Y, Zhang Y, Tao L, Li S, et al. (2014). Essential Oils from Fructus A. zerumbet Protect Human Aortic Endothelial Cells from Apoptosis Induced by Ox-LDL In Vitro. Evid Based Complement Alternat Med, 2014: 956824.
[41] Hung T, Chang HY (2010). Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol, 7: 582-5.
[42] Rinn JL, Chang HY (2012). Genome regulation by long noncoding RNAs. Annu Rev Biochem, 81: 145-66.
[43] Wang KC, Chang HY (2011). Molecular mechanisms of long noncoding RNAs. Mol Cell, 43: 904-14.
[44] Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, et al. (2011). The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res, 71: 3852-62.
[45] Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. (2010). A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 142: 409-19.
[46] Tian D, Sun S, Lee JT (2010). The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell, 143: 390-403.
[47] Yin DD, Zhang EB, You LH, Wang N, Wang LT, Jin FY, et al. (2015). Downregulation of lncRNA TUG1 affects apoptosis and insulin secretion in mouse pancreatic beta cells. Cell Physiol Biochem, 35: 1892-904.
[48] Liao B, Chen R, Lin F, Mai A, Chen J, Li H, et al. (2018). Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/beta-catenin pathway. J Cell Biochem, 119: 2797-2805.
[49] Lang HL, Hu GW, Chen Y, Liu Y, Tu W, Lu YM, et al. (2017). Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3. Eur Rev Med Pharmacol Sci, 21: 959-972.
[50] Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M, Braun T, et al. (2014). Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res, 114: 1389-97.
[51] He C, Yang W, Yang J, Ding J, Li S, Wu H, et al. (2017). Long Noncoding RNA MEG3 Negatively Regulates Proliferation and Angiogenesis in Vascular Endothelial Cells. DNA Cell Biol, 36: 475-481.
[52] Ruan W, Zhao F, Zhao S, Zhang L, Shi L, Pang T (2018). Knockdown of long noncoding RNA MEG3 impairs VEGF-stimulated endothelial sprouting angiogenesis via modulating VEGFR2 expression in human umbilical vein endothelial cells. Gene, 649: 32-39.
[53] Nakamura K, Taguchi E, Miura T, Yamamoto A, Takahashi K, Bichat F, et al. (2006). KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. Cancer Res, 66: 9134-42.
[54] Conigliaro A, Costa V, Lo Dico A, Saieva L, Buccheri S, Dieli F, et al. (2015). CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA. Mol Cancer, 14: 155.
[55] Lang HL, Hu GW, Zhang B, Kuang W, Chen Y, Wu L, et al. (2017). Glioma cells enhance angiogenesis and inhibit endothelial cell apoptosis through the release of exosomes that contain long non-coding RNA CCAT2. Oncol Rep, 38: 785-798.
[56] Kaneko S, Bonasio R, Saldana-Meyer R, Yoshida T, Son J, Nishino K, et al. (2014). Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol Cell, 53: 290-300.
[57] Boon RA, Hofmann P, Michalik KM, Lozano-Vidal N, Berghauser D, Fischer A, et al. (2016). Long Noncoding RNA Meg3 Controls Endothelial Cell Aging and Function: Implications for Regenerative Angiogenesis. J Am Coll Cardiol, 68: 2589-2591.
[58] Chen L, Yang W, Guo Y, Chen W, Zheng P, Zeng J, et al. (2017). Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis. PLoS One, 12: e0185406.
[59] Gutschner T, Hammerle M, Diederichs S (2013). MALAT1 -- a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl), 91: 791-801.
[60] Puthanveetil P, Chen S, Feng B, Gautam A, Chakrabarti S (2015). Long non-coding RNA MALAT1 regulates hyperglycaemia induced inflammatory process in the endothelial cells. J Cell Mol Med, 19: 1418-25.
[61] Maegdefessel L, Rayner KJ, Leeper NJ (2015). MicroRNA regulation of vascular smooth muscle function and phenotype: early career committee contribution. Arterioscler Thromb Vasc Biol, 35: 2-6.
[62] Robinson HC, Baker AH (2012). How do microRNAs affect vascular smooth muscle cell biology? Curr Opin Lipidol, 23: 405-11.
[63] Liu X, Cheng Y, Chen X, Yang J, Xu L, Zhang C (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: 42371-80.
[64] Torella D, Iaconetti C, Catalucci D, Ellison GM, Leone A, Waring CD, et al. (2011). MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ Res, 109: 880-93.
[65] Rangrez AY, M'Baya-Moutoula E, Metzinger-Le Meuth V, Henaut L, Djelouat MS, Benchitrit J, et al. (2012). Inorganic phosphate accelerates the migration of vascular smooth muscle cells: evidence for the involvement of miR-223. PLoS One, 7: e47807.
[66] Yang X, Dong M, Wen H, Liu X, Zhang M, Ma L, 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.
[67] Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, et al. (2007). MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res, 100: 1579-88.
[68] Calvier L, Chouvarine P, Legchenko E, Hoffmann N, Geldner J, Borchert P, et al. (2017). PPARgamma Links BMP2 and TGFbeta1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism. Cell Metab, 25: 1118-1134.e7.
[69] Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C (2009). A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res, 104: 476-87.
[70] Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A (2009). Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem, 284: 3728-38.
[71] Albinsson S, Sessa WC (2011). Can microRNAs control vascular smooth muscle phenotypic modulation and the response to injury? Physiol Genomics, 43: 529-33.
[72] Yu X, Li Z (2014). MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (review). Int J Mol Med, 34: 923-33.
[73] Wang YS, Chou WW, Chen KC, Cheng HY, Lin RT, Juo SH (2012). MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor alpha gene. PLoS One, 7: e30635.
[74] Ma X, Ma C, Zheng X (2013). MicroRNA-155 in the pathogenesis of atherosclerosis: a conflicting role? Heart Lung Circ, 22: 811-8.
[75] Tan M, Yan HB, Li JN, Li WK, Fu YY, Chen W, et al. (2016). Thrombin Stimulated Platelet-Derived Exosomes Inhibit Platelet-Derived Growth Factor Receptor-Beta Expression in Vascular Smooth Muscle Cells. Cell Physiol Biochem, 38: 2348-65.
[76] Salomon C, Yee S, Scholz-Romero K, Kobayashi M, Vaswani K, Kvaskoff D, et al. (2014). Extravillous trophoblast cells-derived exosomes promote vascular smooth muscle cell migration. Front Pharmacol, 5: 175.
[77] Cho JR, Lee CY, Lee J, Seo HH, Choi E, Chung N, et al. (2015). MicroRNA-761 inhibits Angiotensin II-induced vascular smooth muscle cell proliferation and migration by targeting mammalian target of rapamycin. Clin Hemorheol Microcirc, 63: 45-56.
[78] Chen KC, Wang YS, Hu CY, Chang WC, Liao YC, Dai CY, et al. (2011). OxLDL up-regulates microRNA-29b, leading to epigenetic modifications of MMP-2/MMP-9 genes: a novel mechanism for cardiovascular diseases. Faseb j, 25: 1718-28.
[79] Deng L, Blanco FJ, Stevens H, Lu R, Caudrillier A, McBride M, et al. (2015). MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension. Circ Res, 117: 870-883.
[80] Gui T, Zhou G, Sun Y, Shimokado A, Itoh S, Oikawa K, et al. (2012). MicroRNAs that target Ca(2+) transporters are involved in vascular smooth muscle cell calcification. Lab Invest, 92: 1250-9.
[81] Kapustin AN, Chatrou ML, Drozdov I, Zheng Y, Davidson SM, Soong D, et al. (2015). Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circ Res, 116: 1312-23.
[82] Kapustin AN, Schoppet M, Schurgers LJ, Reynolds JL, McNair R, Heiss A, et al. (2017). Prothrombin Loading of Vascular Smooth Muscle Cell-Derived Exosomes Regulates Coagulation and Calcification. Arterioscler Thromb Vasc Biol, 37: e22-e32.
[83] Du Y, Gao C, Liu Z, Wang L, Liu B, He F, et al. (2012). Upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 by miR-29 repression mediates vascular smooth muscle calcification. Arterioscler Thromb Vasc Biol, 32: 2580-8.
[84] Wen P, Cao H, Fang L, Ye H, Zhou Y, Jiang 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: 302-12.
[85] Goettsch C, Rauner M, Pacyna N, Hempel U, Bornstein SR, Hofbauer LC (2011). miR-125b regulates calcification of vascular smooth muscle cells. Am J Pathol, 179: 1594-600.
[86] Mathiyalagan P, Liang Y, Kim D, Misener S, Thorne T, Kamide CE, et al. (2017). Angiogenic Mechanisms of Human CD34(+) Stem Cell Exosomes in the Repair of Ischemic Hindlimb. Circ Res, 120: 1466-1476.
[87] Tan P, Wang YJ, Li S, Wang Y, He JY, Chen YY, et al. (2016). The PI3K/Akt/mTOR pathway regulates the replicative senescence of human VSMCs. Mol Cell Biochem, 422: 1-10.
[88] Zhang L, Zhou M, Wang Y, Huang W, Qin G, Weintraub NL, et al. (2014). miR-92a inhibits vascular smooth muscle cell apoptosis: role of the MKK4-JNK pathway. Apoptosis, 19: 975-83.
[89] Badi I, Burba I, Ruggeri C, Zeni F, Bertolotti M, Scopece A, et al. (2015). MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors. J Gerontol A Biol Sci Med Sci, 70: 1304-11.
[90] He JY, Tu C, Liu YS (2018). Role of lncRNA in aging and age-related diseases. Aging Medicine, 1: 158-75.
[91] Wang Y, Song X, Li Z, Liu B (2018). Long non-coding RNAs in coronary atherosclerosis. Life Sci, 211: 189-197.
[92] Brock M, Schuoler C, Leuenberger C, Buhlmann C, Haider TJ, Vogel J, et al. (2017). Analysis of hypoxia-induced noncoding RNAs reveals metastasis-associated lung adenocarcinoma transcript 1 as an important regulator of vascular smooth muscle cell proliferation. Exp Biol Med (Maywood), 242: 487-496.
[93] Sun Z, Nie X, Sun S, Dong S, Yuan C, Li Y, et al. (2017). Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway. Cell Physiol Biochem, 42: 2569-2581.
[94] Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, et al. (2014). LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation, 130: 1452-1465.
[95] Carrion K, Dyo J, Patel V, Sasik R, Mohamed SA, Hardiman G, et al. (2014). The long non-coding HOTAIR is modulated by cyclic stretch and WNT/beta-CATENIN in human aortic valve cells and is a novel repressor of calcification genes. PLoS One, 9: e96577.
[96] Zhao L, Luo H, Li X, Li T, He J, Qi Q, et al. (2017). Exosomes Derived from Human Pulmonary Artery Endothelial Cells Shift the Balance between Proliferation and Apoptosis of Smooth Muscle Cells. Cardiology, 137: 43-53.
[97] Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, et al. (2012). Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol, 14: 249-56.
[98] Cheng Y, Liu X, Yang J, Lin Y, Xu DZ, Lu Q, et al. (2009). MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation. Circ Res, 105: 158-66.
[99] Chen NX, Kiattisunthorn K, O'Neill KD, Chen X, Moorthi RN, et al. (2013). Decreased microRNA is involved in the vascular remodeling abnormalities in chronic kidney disease (CKD). PLoS One, 8: e64558.
[100] Lin X, He Y, Hou X, Zhang Z, Wang R, Wu Q (2016). Endothelial Cells Can Regulate Smooth Muscle Cells in Contractile Phenotype through the miR-206/ARF6&NCX1/Exosome Axis. PLoS One, 11: e0152959.
[101] Zheng B, Yin WN, Suzuki T, Zhang XH, Zhang Y, Song LL, et al. (2017). Exosome-Mediated miR-155 Transfer from Smooth Muscle Cells to Endothelial Cells Induces Endothelial Injury and Promotes Atherosclerosis. Mol Ther, 25: 1279-1294.
[102] Pfeifer P, Werner N, Jansen F (2015). Role and Function of MicroRNAs in Extracellular Vesicles in Cardiovascular Biology. Biomed Res Int, 2015: 161393.
[103] Bazan HA, Hatfield SA, O'Malley CB, Brooks AJ, Lightell DJr, Woods TC (2015). Acute Loss of miR-221 and miR-222 in the Atherosclerotic Plaque Shoulder Accompanies Plaque Rupture. Stroke, 46: 3285-7.
[104] Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, et al. (2010). Circulating microRNAs in patients with coronary artery disease. Circ Res, 107: 677-84.
[105] Mocharla P, Briand S, Giannotti G, Dorries C, Jakob P, Paneni F, et al .(2013). AngiomiR-126 expression and secretion from circulating CD34(+) and CD14(+) PBMCs: role for proangiogenic effects and alterations in type 2 diabetics. Blood, 121: 226-36.
[106] Jaiswal R, Luk F, Gong J, Mathys JM, Grau GE, Bebawy M (2012). Microparticle conferred microRNA profiles--implications in the transfer and dominance of cancer traits. Mol Cancer, 11: 37.
[107] Feld S, Kjellgren O, Smalling RW (1995). Aggressive interventional treatment of acute myocardial infarction. Lessons from the animal laboratory applied to the catheterization suite. Cardiology, 86: 365-73.
[108] Feng Y, Huang W, Wani M, Yu X, Ashraf M (2014). Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22. PLoS One, 9: e88685.
[109] De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM (2011). Transcoronary concentration gradients of circulating microRNAs. Circulation, 124: 1936-44.
[110] Zile MR, Mehurg SM, Arroyo JE, Stroud RE, DeSantis SM, Spinale FG (2011). Relationship between the temporal profile of plasma microRNA and left ventricular remodeling in patients after myocardial infarction. Circ Cardiovasc Genet, 4: 614-9.
[111] Liew CC, Dzau VJ (2004). Molecular genetics and genomics of heart failure. Nat Rev Genet, 5: 811-25.
[112] Melman YF, Shah R, Das S(2014). MicroRNAs in heart failure: is the picture becoming less miRky? Circ Heart Fail, 7: 203-14.
[113] Ikeda S, Pu WT (2010). Expression and function of microRNAs in heart disease. Curr Drug Targets, 11: 913-25.
[114] Matkovich SJ, Van Booven DJ, Youker KA, Torre-Amione G, Diwan A, Eschenbacher WH, et al. (2009). Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation, 119: 1263-71.
[115] Naga Prasad SV, Duan ZH, Gupta MK, Surampudi VS, Volinia S, Calin GA, et al. (2009). Unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. J Biol Chem, 284: 27487-99.
[116] Wang M, Kim SH, Monticone RE, Lakatta EG (2015). Matrix metalloproteinases promote arterial remodeling in aging, hypertension, and atherosclerosis. Hypertension, 65: 698-703.
[117] Su SA, Xie Y, Fu Z, Wang Y, Wang JA, Xiang M (2017). Emerging role of exosome-mediated intercellular communication in vascular remodeling. Oncotarget, 8: 25700-25712.
[118] Qi Y, Wang X, Rose KL, MacDonald WH, Zhang B, Schey KL, et al. (2016). Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion. J Am Soc Nephrol, 27: 646-56.
[119] Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA (2013). Urinary exosome miRNome analysis and its applications to salt sensitivity of blood pressure. Clin Biochem, 46: 1131-1134.
[120] Cunha PG, Boutouyrie P, Nilsson PM, Laurent S (2017). Early Vascular Ageing (EVA): Definitions and Clinical Applicability. Curr Hypertens Rev, 13: 8-15.
[121] Blum A, Vaispapir V, Keinan-Boker L, Soboh S, Yehuda H, Tamir S (2012). Endothelial dysfunction and procoagulant activity in acute ischemic stroke. J Vasc Interv Neurol, 5: 33-9.
[122] Geng W, Tang H, Luo S, Lv Y, Liang D, Kang X, et al. (2019). Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improving neurogenesis and suppressing microglia activation. Am J Transl Res, 11: 780-792.
[123] Jiang M, Wang H, Jin M, Yang X, Ji H, Jiang Y, et al (2018). Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization. Cell Physiol Biochem, 47: 864-878.
[124] Kubota K, Nakano M, Kobayashi E, Mizue Y, Chikenji T, Otani M, et al. (2018). An enriched environment prevents diabetes-induced cognitive impairment in rats by enhancing exosomal miR-146a secretion from endogenous bone marrow-derived mesenchymal stem cells. PLoS One, 13: e0204252.
[125] Safar ME, London GM, Plante GE (2004). Arterial stiffness and kidney function. Hypertension, 43: 163-8.
[126] Yu Y, Bai F, Qin N, Liu W, Sun Q, Zhou Y, et al. (2018). Non-Proximal Renal Tubule-Derived Urinary Exosomal miR-200b as a Biomarker of Renal Fibrosis. Nephron, 139: 269-282.
[127] Lange T, Stracke S, Rettig R, Lendeckel U, Kuhn J, Schluter R, et al. (2017). Identification of miR-16 as an endogenous reference gene for the normalization of urinary exosomal miRNA expression data from CKD patients. PLoS One, 12: e0183435.
[128] Vogiatzi G, Oikonomou E, Deftereos S, Siasos G, Tousoulis D (2018). Peripheral artery disease: a micro-RNA-related condition? Curr Opin Pharmacol, 39: 105-112.
[129] Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, et al. (2009). MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science, 324: 1710-3.
[130] Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M, et al. (2013). Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res, 113: 322-6.
[131] Geriatric Cardiology Group of Chinese Geriatric Society(2018). Expert consensus on clinical assessment and intervention of vascular aging in China. Chin J Geriatr, 37: 1177-1184.
[132] D'Agostino RBSr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. (2008). General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation, 117: 743-53.
[133] Khoshdel AR, Thakkinstian A, Carney SL, Attia J (2006). Estimation of an age-specific reference interval for pulse wave velocity: a meta-analysis. J Hypertens, 24: 1231-7.
[134] Li SS, Zhang CT, Zhou HL, Huang K, Fsn QP (2012). Correlation of brachial ankle pulse wave velocity with cardiovascular risks and Framingham score. Chin J Mult Organ Dis Elderly, 11: 912-916.
[135] Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, et al. (2014). Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging, 15: 736-46.
[136] Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE (1994). Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol, 24: 471-6.
[137] Wang Y, Tao J, Yang Z, Tu C, Xu MG, Wang JM, et al. (2005). Tumor necrosis factor-α induces release of endothelial microparticle from endothelial cells. Chin J Cardiol, 32: 1137-1140.
[138] Xia WH, Li J, Su C, Yang Z, Chen L, Wu F, et al. (2012). Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men. Aging Cell, 11: 111-9.
[139] Tao J, Wang Y, Yang Z, Tu C, Xu MG, Wang JM (2006). Circulating endothelial progenitor cell deficiency contributes to impaired arterial elasticity in persons of advancing age. J Hum Hypertens, 20: 490-5.
[140] Xitong D, Xiaorong Z (2016). Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases. Gene, 575: 377-384.
[141] Boukouris S, Mathivanan S (2015). Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteomics Clin Appl, 9: 358-67.
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