Table 2.
The mechanism analysis of EVs against PH.
| References | Year | Disease Model | Type of EVs | Target Cell or Tissue | Molecular Mechanism | Therapeutic Effect |
|---|---|---|---|---|---|---|
| [88] | 2018 | Hypoxia | MSC-Exos | Macrophage | Inhibition of macrophage infiltration and reduced the release of inflammatory factors | Reduced hypoxic/ischemic damage |
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| [89] | 2018 | BPD | MSC-Exos | Macrophage | Suppression of the proinflammatory “M1” state and augment of an anti-inflammatory “M2-like” state | Improvement of lung function, decrease in fibrosis and pulmonary vascular remodeling |
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| [74] | 2019 | Sugen/hypoxia | MSC-EVs | Macrophages | Increased the ratio of alternatively to classically activated macrophages (M2/M1) | Normalized RV pressure and reduced RV hypertrophy and muscularization of peripheral pulmonary vessels |
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| [77] | 2016 | MCT | MSC-Exos | Pulmonary arterial | Increased levels of anti-inflammatory, antiproliferative miRs | Prevented any increase in RV/LV; S, WT/D ratios |
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| [90] | 2012 | Hypoxia | MSC-Exos | HPAECs | Increased lung levels of miR-204 and inhibited STAT3 signaling | Exerted a pleiotropic protective effect on the lung |
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| [79] | 2019 | MCTP | ASCs-Exos | HPAECs | miR-191 repressed the expression of BMPR2 | Inhibited HPAECs proliferation |
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| [91] | 2017 | Balloon angioplasty injury on rat carotid arteries | EVs from EC-CM | SMCs | Transferred miR-195 from ECs to SMCs | Inhibited the expression of 5-HTT in SMCs and the proliferation of SMCs. |
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| [50] | 2018 | Cultured BOECs | Exos from BOECs (isolated from patients harboring BMPR2 mutations) | PASMCs | Transferred TCTP from ECs to PASMCs | TCTP overexpression induced proliferation and reduced apoptosis |
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| [9] | 2020 | MCT or hypoxia | MSC-Exos | HPAECs and PASMCs | Upregulated the expression of Wnt5a | The inhibition effect on EndMT and promotion adhesion ability |
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| [10] | 2018 | Hyperoxia-exposed BPD | MSC-Exos | Alveolar | Detected TSG-6 in Exos | Attenuated BPD and its associated pathologies |
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| [76] | 2018 | MCT | MSC-MVs | Lung tissue | Upregulated ACE2 mRNA in the lung tissues and plasma levels of Ang-(1–7) | Exerted beneficial effects against MCT-induced PAH |
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| [92] | 2019 | Hypoxia | MSC-Exos | PASMCs | Increased PASMC expression of PDH and GLUD1 | Improved the mitochondrial dysfunction |
ASCs: adipose-derived mesenchymal stem cells; HPAECs: human pulmonary artery endothelial cells; BMPR2; bone morphogenetic protein receptor 2; MCTP: monocrotaline pyrrole; EC-CM: endothelial cells conditional medium; SMCs: smooth muscle cells; PASMC: pulmonary artery smooth muscle cells; TCTP: translationally controlled tumor protein; BOECs: blood outgrowth endothelial cells; BPD: bronchopulmonary dysplasia; TSG-6: tumor necrosis factor alpha-stimulated gene-6; NAb: neutralizing antibody; PDH: pyruvate dehydrogenase; GLUD1: glutamate dehydrogenase 1.