Table 1.
Summary of the pathological roles of Mφ-EVs in diseases.
| Disease models | EVs source and Isolation methods | EV subtypes (diameter) | Effective molecules | Pathological mechanisms | References |
|---|---|---|---|---|---|
| Cardiovascular | |||||
| Atherosclerosis |
- Mouse peritoneal Mφ with oxLDL - Precipitation |
EVs (40–300 nm) | miR-146a | Decreased migration of naïve macrophages by downregulation of IGF2BP1 and HuR target to β-actin | 70 |
|
- THP-1 cell line with oxLDL - Precipitation |
Exos (30–130 nm) | Not studied | Decreased the growth and tube formation abilities in ECs | 71 | |
|
- THP-1 cell line with oxLDL - Ultracentrifugation |
Exos (undefined) | lncRNA GAS5 | Elevated apoptosis of ECs with increasing expression of expressions of P53, Caspase 3, Caspase 7, and Caspase 9 | 72 | |
|
- J774a.1 cell line with oxLDL - Ultracentrifugation |
EVs (tens to hundreds nm) | Integrins | Enhanced migration and adhesion abilities of VSMC by activating ERK and Akt pathway | 74 | |
|
- RAW264.7 cell line with nicotin - Ultracentrifugation and density gradient fractionation |
Exos (30–100 nm) | miR-21-3p | Enhanced migration and proliferation in VSMC by inhibiting PTEN pathway | 75 | |
| Myocardial infarction |
- Mouse BMDM with Ang II - Ultracentrifugation |
Exos (40–100 nm) | miR-155 |
- Decreased proliferation of cardiac fibroblast by downregulating Ras and ERK expression - Increased inflammatory response in cardiac fibroblast by activating STAT3 pathway |
78 |
| Hypertension |
- THP-1 cell line with Ang II - Ultracentrifugation |
Exos (undefined) | miR-17 | Increased inflammation in ECs by upregulating adhesion molecules ICAM-1 and PAI-1 | 79 |
| Intracranial aneurysm |
- IA patients’ PBMCs with GM-CSF - Ultracentrifugation |
Exos (30–120 nm) | miR-155-5p | Enhanced proliferation and migration of VSMCs by downregulating GERM1 | 80 |
| Metabolic | |||||
| Diabetes |
- Mouse ATM from obesity adipose tissue - Ultracentrifugation |
Exos (30–120 nm) | miR-29a | Impaired insulin sensitivity by inhibiting PPARγ pathway | 86 |
| – | Exos (30–100 nm) | miR-155 | 87 | ||
|
- THP-1 cell line with LPS - Precipitation |
Exos (undefined) | Not studied | Elevated expression of relevant inflammation gene in adipocytes such as CXCL5, SOD, C3, and CD34 | 88 | |
| Premature |
- Mouse BMDM from Ercc1 knockout mice - Ultracentrifugation |
Exos (30–80 nm) | Ercc1− |
- Elevated glucose uptake by increasing GLUT-1 expression in PPCs - Elevated inflammatory response by activating NF-κB in PPCs |
89 |
| Infectious | |||||
| Tuberculosis |
- RAW 264.7 cell line with M.tb - Sucrose gradient centrifugation |
Exos (50–100 nm) | Not studied |
- Elevated inflammatory response in BMM via transmigration of mycobacterial components - Accelerated the formation of granuloma by recruiting and activating Mφ towards lung tissue |
92 |
| Acquired Immune Deficiency Syndrome |
- Human PMDM with HIV-Bal - Iodixanol Gradient |
Exos (undefined)[75] MVs (~300 nm) and Exos (~60 nm)[76] |
HIV-1 viral RNA | Containing abundant viral constituents to uninfected MDM | 93,94 |
|
- Human PMDM with HIV-Bal - Ultracentrifugation |
Enhanced HIV-1 infection by increasing proinflammatory cytokines release | ||||
| Tumor | |||||
| Ovarian cancer |
- THP-1 cell line and human peripheral blood mononuclear cells derived Mφ with M-CSF and IL-4 - Precipitation |
Exos (undefined) | miR-21-5p and miR-29a-3p | Elevated Treg/T17 ratio in CD4+ T cell by suppressing STAT3 pathway to promote tumor growth | 97 |
|
- THP-1 cell line with IL-4 - Precipitation |
Exos (50–150 nm) | miR-223 | Promoted drug resistance by activating PTEN-PI3K/AKT pathways in epithelial ovarian cancer cells | 99 | |
| Pancreatic ductal adenocarcinoma |
- THP-1 cell line with IL-4 - Precipitation |
Exos (~90 nm) | miR-501-3p | Enhanced the migration and invasion of PDAC cells by activating TGF-β pathway leading to tumor formation and metastasis | 98 |
| Fibrosis | |||||
| Tendon injury |
- Mouse BMDM - Ultracentrifugation |
Exos (70–150 nm) | miR-223 | Promoted the fibroblast to myofibroblast transition (EMT) by activating TGF-β pathway | 103 |
| Diabetic nephropathy |
- RAW264.7 cell line with high glucose - Precipitation |
Exos (40–100 nm) | Not studied | 108 | |
| Lung fibrosis |
- RAW264.7 cell line with SiO2 - Ultracentrifugation |
Exos (30–150 nm) | miR-125a-5p | 105 | |
|
- Rat primary peritonea macrophages with IL-4 - Precipitation |
Exos (undefined) | miR-328 | 106 | ||
|
- THP-1 cell line with PMA and asbestos - Not given |
Exos (undefined) | lncRNA-ASLNCS5088 | 107 | ||
|
- THP-1 cell line with PMA and asbestos - Precipitation |
Exos (undefined) | Not studied | Up-regulated genes hCCNB2, hEGR1, and hFANCD2; down-regulated genes hCRELD2, hERO1B, and hJAG1 in mesothelial cells | 104 | |
| Diabetes cardiac dysfunction |
- RAW264.7 cell line with high glucose and BMDM from diabetes mice - Precipitation |
Exos (undefined) | HuR protein | Increased inflammatory response and fibrogenesis in cardiac fibroblasts | 109 |