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 | |
- THP-1 cell line with oxLDL - Precipitation | Exos (30–130 nm) | Not studied | Decreased the growth and tube formation abilities in ECs | ||
- 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 | ||
- 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 | ||
- 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 | ||
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 | |
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 | |
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 | |
Metabolic | |||||
Diabetes | - Mouse ATM from obesity adipose tissue - Ultracentrifugation | Exos (30–120 nm) | miR-29a | Impaired insulin sensitivity by inhibiting PPARγ pathway | |
– | Exos (30–100 nm) | miR-155 | |||
- 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 | ||
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 | |
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 | |
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 | |
- 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 | |
- 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 | ||
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 | |
Fibrosis | |||||
Tendon injury | - Mouse BMDM - Ultracentrifugation | Exos (70–150 nm) | miR-223 | Promoted the fibroblast to myofibroblast transition (EMT) by activating TGF-β pathway | |
Diabetic nephropathy | - RAW264.7 cell line with high glucose - Precipitation | Exos (40–100 nm) | Not studied | ||
Lung fibrosis | - RAW264.7 cell line with SiO2 - Ultracentrifugation | Exos (30–150 nm) | miR-125a-5p | ||
- Rat primary peritonea macrophages with IL-4 - Precipitation | Exos (undefined) | miR-328 | |||
- THP-1 cell line with PMA and asbestos - Not given | Exos (undefined) | lncRNA-ASLNCS5088 | |||
- 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 | ||
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 | |
