Table 2.
The EV-miRNAs in the pathogenesis of HF.
| Pathological Phenotype | miRNA | Cell Source | Target Cell | Potential Functional Mechanism | Ref. |
|---|---|---|---|---|---|
| Cardiac hypertrophy | miRNA-21-3p | CF | CM | Translational inhibition of both SORBS2 and PDLIM5 | [41] |
| miRNA-27a-5p | CF | CM | Translational inhibition of PDLIM5 | [42] | |
| miRNA-27a-3p, miRNA-28-3p miRNA-34a | CF | CM | Dysregulation of Nrf2/ARE signaling and oxidative stress | [99] | |
| miR-200a | Adipocyte | CM | Selective activation of PPARγ signaling and decreased TSC1 and subsequent mTOR activation | [100] | |
| miRNA-208a | CM | CM | Repression of Thrap1 and myostatin expression | [101,102] | |
| miRNA-217 | CF | CM | Targeting PTEN | [103] | |
| Cardiac fibrosis | miRNA-208a | CM | CF | Targeting Dyrk2 to promote NFAT dephosphorylation and nuclear translocation | [104] |
| miRNA-217 | CM | CF | Targeting PTEN | [103] | |
| miRNA-494-3p | CM | CF | Targeting PETN to enhance the phosphorylation of AKT, ERK, and SMAD2/3 | [105] | |
| miRNA-218-5p | CM | CF | Targeting TNFAIP3 to activate TGF-β signaling | [106] | |
| miRNA-23a-3p | Adipocyte | CF | Targeting RAP1 | [107] | |
| miR-142-3p | Activated CD4+ T cell | CF | Targeting APC to activate the WNT signaling pathway | [108] | |
| miRNA-21 | MP and/or CM | CF | Targeting Spry1 to augment ERK-MAP kinase activity | [109,110,111,112,113] | |
| Angiogenesis | miRNA-200c-3p | CM | EC | Impaired endothelial migration and tube formation, as well as a lower proliferation capacity | [114] |
| miRNA-29a | CM | EC | Inhibiting the proliferation, migration, and angiogenic ability of cardiac microvascular ECs | [115] | |
| miRNA-200a-3p | Activated CF | EC | Targeting ETS1/VEGF-A signaling axis | [116] | |
| miRNA-155 | Activated MP | EC | Targeting Sirt1/AMPKα2 and RAC1–PAK2 signaling pathways | [117] | |
| Inter-organ communications | miRNA-1 | CM | Neuron | Targeting TPPP/p25 to disturb the stability of neuronal microtubules | [102,118] |
| miRNA-27a-3p, miRNA-28-3p and miRNA-34a | CM and/or CF | Neuron | Targeting Nrf2/ARE signaling to induce oxidative stress and subsequently elicit sympathetic excitation | [49] | |
| miRNA-126 | EC | NEUT | Transcriptional activation of NEUTs and contribution to cardiac inflammation and chemokine production | [48,119,120] |
Abbreviations: adenomatous polyposis coli (APC), cardiac fibroblast (CF), cardiac myocyte (CM), dual-specificity tyrosine phosphorylation-regulated kinase 2 (Dyrk2), endothelial cell (EC), ETS Proto-Oncogene 1 (ETS1), macrophages (MP), neutrophils (NEUTs), nuclear factor of activated T cells (NFAT), Ras-related protein 1 (RAP1), Sprouty homolog 1 (Spry1), thyroid hormone-associated protein 1 (Thrap1), tuberous sclerosis complex (TSC1), tubulin polymerization promoting protein (TPPP/p25).