Table 3.
Exo-ncRNAs as potential diagnostic biomarkers and therapeutics approaches in pathogenic mechanism of AF.
| Exo-ncRNAs | Origination | Effect | Mechanisms | References |
|---|---|---|---|---|
| Exo-miR-92b-3p/Exo-miR-1306-5p/Exo-miRlet-7b-3p | Plasma | Diagnostic | These miRNAs and target genes were involved in the process of AF through affecting biological processes such as energy metabolism, lipid metabolism, inflammation, and enzyme activity | (178) |
| Exo-miR-483-5p/Exo-miR-142-5p/Exo-miR-223-3p | Plasma | Diagnostic | Some of the pathways are related with myocardial remodeling (PI3K-Akt signaling pathway, adrenergic signaling in cardiomyocytes, focal adhesion, Wnt signaling pathway, calcium signaling pathway) and oxidative stress (MAPK signaling pathway, oxytocin signaling pathway) | (198) |
| Exo-miRNA-103a/Exo-miR-107/Exo-miR-320d/Exo-miR-486/Exo-miR-let-7b | Serum | Diagnostic | These miRNAs were involved in atrial function and structure (e.g., gap junction, adherens junction, adrenergic signaling), oxidative stress (e.g., MAPK, AMPK), fibrosis (e.g.,Wnt, hypoxia inducible factor-1), and other pathways | (180) |
| Exo-miR-382-3p/Exo-miR-450a-2-3p/Exo-miR-3126-5p | Pericardial fluid | Diagnostic | Implicated in cardiac fibrosis-related pathways, including the hypoxia-inducible factor-1 (HIF1), mitogen activated protein kinase (MAPK), and adrenergic and insulin pathways | (181) |
| Exo-Let-7c | MSCs | Treatment | Anti fibrosis, regulating the TGF-β/Smad | (183) |
| Exo-miR-17 | CPCs | Treatment | Anti fibrosis, inhibit the TGF-β-induced fibrosis under oxidative stress | (184) |
| Exo-miR-19a | MSCs | Treatment | 1) Anti-apoptosis, inhibit oxidative stress-induced apoptosis by targeting three prime untranslated regions in cylindromatosis, subsequently achieving the protective effect. 2) Anti-inflammation, decrease the expression of the inflammatory cytokines, moreover, pro-inflammatory/anti-inflammatory factors were down-regulated/up-regulated. 3) Anti fibrosis, downregulates the expression of the target proteins in CMs, PTEN, and Bcl-2-like protein, and activates the Akt and ERK signaling pathways | (71, 200) |
| Exo-miR-21 | CPCs/ iPSCs/MSCs | Treatment | 1) Anti-apoptosis, ameliorate the CMs apoptosis, which may relate to the inhibition of caspase 3/7 mediated apoptosis by the miR-21/PDCD4 signal axis. 2) Angiogenesis, induce angiogenesis and improve the cardiac cells' survival via inhibiting the PTEN/Akt pathway | (196, 197, 209) |
| Exo-miR-22 | BMMSCs | Treatment | Anti fibrosis and anti-apoptosis, target the Mecp2 to alleviate fibrosis and inhibit apoptosis | (185) |
| Exo-miR-24-3p | MSCs | Treatment | Anti-apoptosis, decrease apoptosis and promote the CMs proliferation | (201) |
| Exo-miR-25-3p | BMMSCs | Treatment | 1) Anti-inflammation, inhibit the inflammatory cytokines expression. 2) Anti-apoptosis, inhibit apoptosis by Ezh2/Socs3 | (22) |
| Exo-miR-26a | Muscle | Treatment | Anti fibrosis, blunt the FOXO1 activation and inhibit cardiac fibrosis | (195) |
| Exo-miR-125b | BMMSCs | Treatment | 1) Anti-apoptosis and 2) anti-inflammation, had the ability of anti-apoptosis and inhibit the inflammatory cytokines expression | (204) |
| Exo-miR-126 | CD133+ cells/ CFs/ADSCs | Treatment | 1) Anti fibrosis, reduce VCAM, SPRED-1, and MCP1, and subsequently decrease the interstitial fibrosis. 2) Anti fibrosis, inhibit fibrosis by targeting the f TGF-β and collagen I. Anti-apoptosis, reduce apoptosis in neonatal rats cardiomyocytes and improve cell survival by targeting ERRFI1. 3) Angiogenesis, promote the generation of microvascular cells and the migration of endothelial progenitor cells, through enhancing the VEGF pathway via the suppression of angiogenesis inhibitors SPRED1 and PI3KR2 | (190, 192, 211) |
| Exo-miR-132 | CDCs | Treatment | 1) Angiogenesis, inducing capillary-like tube formation and enhancing the migration and proliferation of HUVEC, through suppressing the expression of the Efna3 and RASA1 | (221) |
| Exo-miR-133a | NA | Treatment | 1) Anti-apoptosis, inhibits apoptosis in myocardial ischemic postconditioning, prevents the expression of TAGLN2 and caspase-9, and upregulates the expression of antiapoptotic protein Bcl-2 | (201) |
| Exo-miR-144 | MSCs | Treatment | Anti-apoptosis, target the PTEN/AKT pathway, and thus improve the apoptosis of the CMs | (202) |
| Exo-miR-146a | ADSCs/DCs/ CDCs | Treatment | 1) Anti fibrosis, down regulating the gene EGR1. 2) Anti-inflammation, regulated the inflammatory response by inhibiting the IRAK-1. 3) Anti-apoptosis, targeting of Irak-1 and Traf6, both involved in the toll-like receptor (TLR) signaling pathway | (182, 210, 215, 231) |
| Exo-miR-155 | Macrophage/ECs | Treatment | 1) Anti fibrosis, decrease fibroblast proliferation by inhibiting the SOS-1. 2) Anti-inflammation, can polarize macrophages to M2 cells, inhibit inflammatory reactions (KLF2/miR-155) | (191, 232) |
| Exo-miR-155-5p | Serum | Treatment | 1) Anti fibrosis, enhances the S1PR1 and inhibits the SOCS1/STAT3 signaling pathway, thereby reducing the 2) Anti-inflammation, reduce the IL-6 and IL-17 in the valve tissue and serum | (214) |
| Exo-miR-181a | MSCs | Treatment | Anti-inflammation, create an anti-inflammatory environment and increase the Tregs polarization | (213) |
| Exo-miR-185 | BMMSCs | Treatment | Anti-apoptosis and anti-inflammation, had the ability of anti-apoptosis targeting Socs2 | (207) |
| Exo-miR-210 | CPCs/MSCs | Treatment | 1) Anti fibrosis, inhibit the TGF-β-induced fibrosis under oxidative stress. 2) Anti-apoptosis, downregulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. 3) Angiogenesis, inducing capillary-like tube formation and enhancing the migration through suppressing the expression of the Efna3 and RASA1 | (184, 205, 219, 220) |
| Exo-miR-221 | MSCs | Treatment | Anti-apoptotic by inhibiting the P53 and Bcl-2b and reducing the methylation of CpG binding protein-2 | (206) |
| Exo-miR-223 | BMMSCs | Treatment | Anti-inflammation, induce the expression of ICAM-1 to inhibit the inflammatory reaction | (218) |
| Exo-miR-320 | CMs | Treatment | Anti fibrosis, negatively affect the proliferation and migration of ECs | (188) |
| Exo-miR-320d | ADSCs | Treatment | Anti-apoptosis, negatively regulated STAT3 expression, indirectly inhibited CMs apoptosis in AF, and increased survival, providing new insights into treatment strategies of AF | (17) |
| Exo-miR-423-3p | CFs | Treatment | Anti-apoptosis, improve the viability of the H2C9 and reduce apoptosis by targeting the RAP2C | (212, 213) |
| Exo-miR-290/Exo-miR-294/Exo-miR-295 | ESCs | Treatment | Anti fibrosis, anti-apoptosis and angiogenesis, increases neovascularization improves cardiomyocyte survival and reduces fibrosis. Enhances cardiac progenitor cell survival and proliferation, as well as cardiac commitment | (186) |
| Exo-miR-378/Exo-miR-29a/Exo-miR-29b/Exo-miR-455 | CMs | Treatment | Anti fibrosis, reducing the collagen and MMP9 via inhibiting the MAPK and Smad pathways | (187) |
| Exo-miR-425/Exo-miR-744 | Serum | Treatment | Anti fibrosis, inhibit fibrosis by targeting the f TGF-β and collagen I | (193, 194) |
| Exo-miR-181b/Exo-miR-182 | CDCs/MSCs | Treatment | Anti-inflammation, reduce PKCδ transcription. Promoted the polarization of M2 macrophages and thereby alleviated the inflammatory response | (216, 217) |
| Exo-miR-150-5p/Exo-miR-142-3p/Exo-Let-7d | Tregs | Treatment | Anti-inflammation, reduce the immune reactions, and suppress the Th1 proliferation and secretion of the pro-inflammatory cytokines | (209, 223) |
| Exo-lncRNA Mhrt | ND | Treatment | Anti fibrosis, inhibit cardiac fibrosis and cardiac myocyte hypertrophy | (199) |
CMs, cardiomyocytes; ECs, Endothelial cells; CFs, Cardiac fibroblasts; CDCs, cardiosphere derived cells; MSCs, cardiac progenitor cells; ESCs, Embryonic stem cells; ADSCs, adipose-derived stem cells; BMMSCs, bone marrow derived cardiac progenitor cells; CPCs, cardiac progenitor cells; iPSCs, induced pluripotent stem cells. ND, Not Determined.