Table 2.
Potential benefits of extracellular vesicles as therapeutic drugs in calcification
| Extracellular vesicles origin | Molecular mediators in EVs | Stimulus | Mechanisms | Effects | Refs |
|---|---|---|---|---|---|
| Aged bone-EVs | - | Alendronate | Alendronate down-regulated the release of EVs | Reduced the ovariectomy-induced VC | [10] |
| BMSC-EVs | - | - | EVs alter the miRNAs of VC-related mTOR, MAPK and Wnt signaling pathways in HA-VSMCs | Alleviated high Pi-induced VC | [187] |
| BMSC-EVs | miR-15a/15b/16 | - | Transfer of miR-15a/15b/16 into VSMCs subsequently inhibited target NFATc3 and further downregulated OCN expression | Inhibited osteogenic transdifferentiation and calcification of VSMC | [188] |
| BMSC-EVs | miR-381-3p | - | Transfer of miR-381-3p into VSMCs downregulated NFAT5 | Improved apoptosis and VC in CKD-VC | [189] |
| BMSC-EVs | miR-146a | AGEs-BSA | Transfer of high levels of miR-146a into VSMCs downregulated TXNIP expression | Inhibited AGEs-BSA-mediated VC | [193] |
| BMSC-EVs | - | - | Transfer of EVs into VSMCs regulated the NONHSAT 084969.2/NF-κB axis | Inhibited pi-induced VSMC transdifferentiation and calcification | [190] |
| BMSC-EVs | - | - | Transfer of EVs into VSMCs regulated the SIRT6-HMGB1 deacetylation pathway | Inhibited high Pi-induced aortic calcification | [191] |
| VSMC-exosomes | - | PT and PT activation products | Inhibited of nucleation sites on the surface of EVs | Prevented exosome-mediated VC | [235] |
| VSMC-MVs | - | Anti-sortilin | Anti-sortilin treatment inhibited the formation of hypermineralizable MVs | Prevented Nε-Carboxymethyl-lysine (CML)-induced diabetic atherosclerotic calcification | [69] |
| VSMC-EVs | Osteogenic phenotype-related proteins | GFOGER peptide | GFOGER peptide regulated the content of proteins associated with osteogenic phenotype in EVs and prevented EVs-col 1 interaction | Inhibited osteogenic transformation of VSMCs | [242, 243] |
| VSMC- EVs | miR-92b-3p | Curcumin | Curcumin increased miR-92b-3p loading in EVs and decreased expression of its target KLF4 | Inhibited vitamin D3-induced VC | [245] |
| VSMCs/CVSMCs-EVs | miR-204/ miR-211 | Melatonin | Melatonin upregulated miR-204/ miR-211 in EVs | Reduced the osteogenic differentiation and senescence of VSMCs/CVSMCs | [71] |
| VSMC-EVs | - | Verapamil | Verapamil inhibited ALP activity of calcified EVs and reduced the ability of EVs to subsequently calcify on COL 1 | Prevented ECM mineralization | [306] |
| VSMC-EVs | - | Bisphosphonates | Maybe the pyrophosphate-like activity of BiP | BiP blocked EV aggregation and altered existing mineral growth | [311] |
| VSMC-EVs | MGP and Annexin A2 | BGP-15 | BGP-15 increased MGP content and decreased Annexin A2 content in EVs and prevented calcium deposition in the extracellular matrix | Inhibited Pi-induced osteochondrogenic phenotypic transition and mineralization in VSMCs under either NG or HG | [307] |
| HUVEC-EVs | miR-126-5p | AGEs | AGEs stimulated the secretion of mir-126-5p-rich EVs | Inhibited diabetic medial calcification | [70] |
| Telocytes-EVs | - | - | EVs promoted miR-30b expression and inhibited Runx2 expression and the Wnt/β-catenin pathway after uptake by calcified valve tissues and cells | Improved aortic valve calcification | [272] |
| Human placenta-derived MSCs-sEVs | VEGF, miR-126 and miR-145 | - | EVs induced macrophages to shift from a M1(AS-causing phenotype) and to a M2(anti-osteogenic phenotype) and are enriched for VEGF, miR-126 and miR-145 | Inhibited thrombosis and calcification to enhance the patency of vascular grafts and increased regeneration of endothelium and smooth muscle | [312] |
| Plasma-EVs | miR-223 | mOL-HDF | mOL-HDF treatment reduced the expression of miR-223 in EVs | Inhibited osteogenic differentiation of VSMCs | [259] |