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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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Abstract  

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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http://www.aginganddisease.org/EN/10.14336/AD.2019.0402     OR     http://www.aginganddisease.org/EN/Y2020/V11/I1/164
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]
miR-17ANGPT1
STAT3
pro-proliferation, pro-migration,
anti-inflammation
[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-223ICAM-1anti-inflammation[34]
miR-125aDLL4pro-angiogenesis[36]
miR-181b-5pTRPM7pro-angiogenesis[37]
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,
pro-angiogenesis
[49]
MALAT1IL-6, TNF-α, SAA3anti- proliferation, pro-migration,
pro-inflammation
[50]
[59, 60]
HOTAIRVEGFpro-angiogenesis[53]
H19Unknownpro-angiogenesis[54]
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-21BCL2pro-proliferation[67]
miR-130aBMP2, TGFβ1pro-proliferation[68]
miR-221/222p27, p57pro-proliferation[69, 70]
miR-152DNMT1anti-proliferation[73]
miR-155Ets1anti-proliferation[74]
miR-223PDGFRβanti-proliferation[75]
miR-339PDGFRβanti-proliferation[75]
miR-21PDGFRβanti-proliferation[75]
miR-29bDNMT3bpro-migration[78]
miR-143-3pTGFβpro-migration, pro-angiogenesis[79]
miR-712NCKX4pro-calcification[80]
miR-714PMCA1pro-calcification[80]
miR-762NCX1pro-calcification[80]
miR-29a/bADAMTS-7anti-calcification[83]
miR-125bEts1, Osterixanti-transdifferentiation,
anti-calcification
[84, 85]
miR-126-3pVEGF, ANG1, ANG2, MMP9, TSP1pro-angiogenesis[86]
miR-92aMKK4anti-apoptosis, anti-senescence[88]
miR-34aSIRT1pro-senescence[89]
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.
CargoDiseaseFunctions
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.
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