Table 2.
Overview of published studies on body fluids-based exosomes and their mediators in CVDs, risk factors, and complications.
| Cardiovascular Disease |
Isolation Method | Biofluid | Discovery Cohort Size | Exosome Validation Method | Exosomes Characteristics | Biomarker Candidate(s) | Ref. |
|---|---|---|---|---|---|---|---|
| Coronary artery disease (CAD) | ExoQuick Exosome Precipitation Solution | Plasma | C57BL/6 mice, n = 5 |
Electron microscopy Nanoparticle tracking analysis Western Blotting |
n. d. | miR-1, miR-208a, miR-133a, miR-499-5p | [70] |
| Ultracentrifugation (sucrose) | Serum | Human, n = 5 | Electron microscopy CD9 staining |
n. d. | MYBPC3, VIM | [71] | |
| n. d. | Plasma | Tandem stenosis group, mice n = 4 | n. d. | n. d. | miR-223, miR-339, miR-21 | [72] | |
| Ultracentrifugation | Plasma | Tandem stenosis group, mice n = 4 | Electron microscopy Western blotting |
n. d. | miR-223, miR-339, miR-21 | [73] | |
| Ultracentrifugation | Plasma | Human, n = 25 | Mass spectrometry for proteome analysis, using nano–liquid chromatography LTQ Orbitrap XL mass spectrometer | n. d. | n. d. | [74] | |
| Acute myocardial infarction (AMI) | ExoQuick Exosome Precipitation Solution | Plasma | C57BL/6 mice, n = 5 |
Electron microscopy Nanoparticle tracking analysis Western Blotting |
n. d. | miR-1, miR-208a, miR-133a, miR-499-5p | [70] |
| ExoQuick Exosome Precipitation Solution | Serum | Human, n = 28 | Transmission electron microscopy Flow cytometry Immunoblotting |
CD63 expression | miR-30a | [75] | |
| Ultracentrifugation | Plasma; Pericardial fluid | Human, n = 12 | Western Blotting | Rab 5B and CD81 expression | n. d. | [76] | |
| Ultracentrifugation | Serum | Human, n = 10 | n. d. | n. d. | Apo-J | [77] | |
| Coronary artery dilatation due to Kawasaki disease (KD) | ExoQuick Exosome Precipitation Solution | Serum |
Human, n = 6 |
Transmission electron microscopy Western blotting |
CD9, CD81, and flotillin expression | ITIH4, PROS1, C9, AFM, A1BG IGFALS, C4A, HPX, SERPINC 1, Inter-alpha (Globulin) inhibitor H4 (Plasma Kallikrein-sensitive glycoprotein) variant, AGT, DBP, KNG1, SERPINA 3, LRG1, C4B, HP, CLU, PON3, C3, CD5L, SHBG, FGG, APOL1, CFHR1, FGB, TF, ALB, CFI, IGHM, ALB isoform CRA_k, IGKVA-1, MBL2, TTR, IGKC, APOM, SERPINA 1, CLEC3B |
[78] |
| Acute heart failure (HF) | Exosome isolation kit | Serum | Human, n = 43 | Electron microscopy Nanoparticle tracking analysis Western Blotting |
CD63 and Hsp70 expression | miR-92b-5p, miR-192-5p, miR-320a | [79] |
| Exosome isolation kit | Serum | Human, n = 28 | Electron microscopy Nanoparticle tracking analysis Western blotting |
Size: 40–150 nm (average 80 nm); CD63 and Hsp70 expression |
miR-92b-5p, miR-192-5p, miR-320a | [80] | |
| HF | ExoQuick Exosome Precipitation Solution | Serum | Human, n = 4 | Western Blotting | CD63 expression | miR-192, miR-194, miR-34a | [81] |
| Ultracentrifugation | Pericardial fluid | Human, n = 51 | n. d. | n. d. | miR-210, let-7b-3p, let-7d-3p, miR-1, miR-125a-5p, miR-126-3p, miR-129-5p, miR-132-3p, miR-133a, miR-135a-5p, miR-135b-5p, miR-138-5p, miR-139-5p, miR-140-5p, miR-143-3p, miR-145-5p, miR-146a-3p, miR-146a-5p, miR-17-5p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-208a, miR-20a-5p, miR-21-3p, miR-214-3p, miR-23a-3p, miR-23b-3p, miR-25-3p, miR-30a-3p, miR-30c-5p, miR-30e-3p, miR-320a, miR-330-5p, miR-339-3p, miR-346, miR-34c-3p, miR-365a-3p, miR-375, miR-499a-5p, miR-505-3p, miR-532-3p, miR-671-5p, miR-92b-3p, miR-9-3p | [82] | |
| Exosome Isolation kit | Plasma | Human, n = 40 | n. d. | n. d. | miR-486, miR-146a | [83] | |
| Idiopathic pulmonary arterial hypertension (IPAH) | Ultracentrifugation | Plasma | Human, n = 5 | Nanoparticle tracking analysis BCA Protein assay Immunoblotting |
CD31, CD63 and TSG101 expression | n. d. | [84] |
| Ultracentrifugation | Plasma | Human, n = n. d. | Nanoparticle tracking analysis Transmission electron microscopy Western blotting |
n. d. | miR-let-7c, miR-let-7d, miR-16, miR-18a, miR-19b, miR-20a, miR-20b, miR-27b, miR-30b, miR-30c, miR-125a-5p, miR-145, miR-146b. miR-148a, miR-195, miR-200b, miR-215, miR-218, miR-221, miR-339-3p, miR-365 |
[85] | |
| Arterial disease/ cardiovascular risk factors | ExoQuick Exosome Precipitation Solution | Plasma | Human, n = 1012 | BCA Protein assay | n. d. | n. d. | [86] |
| (i) Hypertension | Exosome isolation kit | Plasma | Spontaneous hypertensive rats (SHRs), n = n. d. | Dynamic light scattering Western blotting |
Size: 10–200 nm diameter (those ranging 30–150 nm accounted for 80%); CD63 and Hsp70 expression | rno-miR-148a-3p, rno-miR-122-5p, rno-miR-143-3p, rno-miR-192-5p, rno-let-7i-5p, rno-miR-215, rno-miR-140-3p, rno-miR-99a-5p, rno-miR-6329, rno-miR-378a-3p, rno-miR-486, rno-miR-378a-5p, rno-miR-6328, rno-miR-187-3p, rno-miR-383-5p, rno-miR-206-3p, rno-miR-425-5p, rno-miR-128-3p, rno-miR-181c-3p, rno-let-7d-5p, rno-miR-191a-3p, rno-miR-185-5p, rno-miR-218a-5p, rno-let-7f-5p, rno-miR-148a-5p, rno-miR-322-3p, rno-miR-181d-5p, rno-miR-223-5p, rno-miR-191a-5p, rno-miR-17-5p, rno-miR-3559-5p, rno-let-7a-5p, rno-miR-15b-5p, rno-miR-223-3p, rno-miR-872-5p, rno-miR-3068-3p |
[87] |
| Ultracentrifugation | Serum | Cardiac hypertrophic Wistar rats, n = 6 | Electron microscopy Western blotting |
n. d. | HSP90, HSC70, CD63, CD9, GAPDH, CD68, miR-17-3p, miR-145-5p, miR-221-3p, miR-222-5p |
[88] | |
| n. d. | Urine | C57BL6J/Ola mice, n = n. d. |
Nanoparticle tracking analysis Western blotting |
n. d. | NCC | [89] | |
| Ultracentrifugation | Urine | Human, n = 11 | n. d. | n. d. | RAIG-2, SDCBP, NKCC2, TSC, ACTB, RAIG-3, ANPEP, GAPDH, MME, EZR, KRT1, ENO1, LDHB, HSPA8, ANXA2 | [90] |
|
| (ii) Obesity | n. d. | Plasma | Human, n = 23 | n. d. | n. d. | miR-122 | [91] |
| (iii) Type 2 diabetes (T2D) | ExoQuick Exosome Precipitation Solution | Serum | Human, n = 33 | n. d. | n. d. | miR-122-5p, let-7a-3p, miR-26b-3p, miR-193b-5p, miR-4532, miR-432-5p, let-7f-1-3p, miR-183-5p, miR-3656, miR-340-3p, miR-6751-3p, miR-1273a, miR-4484, miR-8485, miR-4644, miR-1273g-3p, miR-4271, miR-7847-3p, miR-4461, miR-6885-5p |
[92] |
| ExoQuick Exosome Precipitation Solution | Plasma | Human, n = 18 | n. d. | n. d. | miR-326, miR-532-5p, miR-186, miR-127-3p, let-7g, let-7d, miR-126, miR-101, miR-18b, miR-21, miR-199a-3p, miR-502-3p, miR-495, miR-132, miR-15b, miR-200c, miR-223-5p, miR-16, miR-543, miR-195, let-7a, miR-26b, miR-374a, miR-26a, let-7f, ADIPOR1, ADIPOR2, APPL1 |
[93] | |
| (iv) Diabetic nephropathy | ExoQuick Exosome Precipitation Solution | Serum | Human, n = 33 | n. d. | n. d. | miR-122-5p, miR-432-5p, miR-3656, miR-193b-5p, miR-6087, miR-4488, miR-26b-3p, miR-8485, miR-23a-5p, miR-4532, let-7a-3p, miR-6739-5p, miR-1273a, miR-7641, miR-4461, miR-6751-3p, miR-4484, miR-7847-3p, miR-1273g-3p, miR-140-5p |
[92] |
| (v) Familial hypercholesterolemia (with a CV event) | Filtration | Plasma | Human, n = 42 | Nanoparticle tracking analysis Flow cytometry (CD63 and CD81) |
n. d. | miR-130b, miR-133a, miR-142-3p, miR-200c, miR-324-5p, miR-339-3p, miR-425-5p, miR-660, miR-744, miR-122 |
[94] |
| (vi) Obstructive sleep apnea (OSA) | Exosome isolation kit | Plasma | Human, n = 8 | Electron microscopy Western blotting |
n. d. | hsa-miR-16-5p, hsa-miR-4459, hsa-miR-451a, hsa-miR-6510-5p |
[95] |
| Exosome isolation kit | Plasma | Human, n = n. d. | Electron microscopy Flow cytometry Western blotting |
CD63 expression | n. d. | [96] | |
| Exosome isolation kit | Plasma | Human, n = 10 | Electron microscopy | n. d. | n. d. | [97] | |
| Myocardial ischemia/reperfusion (IR) | ExoQuick Exosome Precipitation Solution | Plasma | Human, n = 4 | Transmission electron microscopy BCA Protein assay Flow cytometry Western blotting |
Cup-shaped membrane-bound vesicles;size: ~100 nm diameter; CD63, CD9 and CD81 expression | miR-24, miR-21, miR-214, miR-132, miR-195, miR-210, miR-144, miR-150, miR-34a |
[98] |
| Ultracentrifugation | Serum | MI Wistar rats, n = 3 | BCA Protein assay Western blotting |
CD9 and Hsp90 expression | miR-21, miR-29a, miR-30a, miR-133a |
[99] | |
| Coronary artery bypass graft (CABG) |
Column-based system | Plasma | Human, n = 21 | Nanoparticle tracking analysis Transmission electron microscopy Western blotting |
n. d. | miR-1, miR-23a, miR-24, miR-92a, miR-126, miR-133a, miR-133b, miR-208a, miR-208b, miR-210, miR-223, miR-451 |
[100] |
Legend: CAD, coronary artery disease; MYBPC3, myosin-binding protein C, cardiac-type; VIM, vimentin; LTQ, linear trap quadrupole; AMI, acute myocardial infarction; Rab 5B, Ras-related protein Rab-5B; Apo-J, apolipoprotein J; KD, Kawasaki disease; ITIH4, inter-alpha-trypsin inhibitor heavy chain H4; PROS1, vitamin K-dependent protein S; C9, complement component C9; AFM, afamin; A1BG, alpha-1B-glycoprotein; IGFALS, insulin-like growth factor-binding protein complex acid labile subunit; C4A, complement C4-A; HPX, hemopexin; SERPINC 1, antithrombin-III; AGT, angiotensinogen; DBP, vitamin D-binding protein; KNG1, kininogen-1; SERPINA 3, alpha-1 antichymotrypsin; LRG1, leucine-rich alpha-2-glycoprotein; C4B, complement C4-B; HP, haptoglobin; CLU, clusterin; PON3, serum paraoxonase/lactonase 3; C3, complement C3; CD5L, CD5 antigen-like; SHBG, sex hormone-binding globulin; FGG, fibrinogen gamma chain; APOL1, apolipoprotein L1; CFHR1, complement factor H-related protein 1; FGB, fibrinogen beta chain; TF, serotransferrin; ALB, serum albumin; CFI, complement factor I; IGHM, immunoglobulin heavy constant mu; IGKVA-1, immunoglobulin kappa variable 4-1; MBL2, mannose-binding protein C; TTR, transthyretin; IGKC, immunoglobulin kappa constant; APOM, apoliprotein M; SERPINA 1, alpha-1-antitrypsin; CLEC3B, tetranectin; HF, heart failure; DCM, dilated cardiomyopathy; HSP70, heat shock protein 70; IPAH, idiopathic pulmonary arterial hypertension; BCA, bicinchoninic acid; TSG101, tumor susceptibility gene 101 protein; SHRs, spontaneous hypertensive rats; HSP90, heat shock protein 90; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; NCC, sodium chloride cotransporter; RAIG-2, retinoic acid-induced gene 2 protein; SDCBP, syntenin-1; NKCC2, solute carrier family 12 member 1; TSC, solute carrier family 12 member 3; ACTB, actin, cytoplasmic 1; RAIG-3, G-protein coupled receptor family C, group 5, member C; ANPEP, aminopeptidase N; MME, neprilysin; EZR, ezrin; KRT1, keratin, type II cytoskeletal 1; ENO1, alpha-enolase; LDHB, L-lactate dehydrogenase B chain; HSPA8, Heat shock cognate 71 kDa protein; ANXA2, Annexin A2; T2D, type 2 diabetes; ADIPOR1, adiponectin receptor 1; ADIPOR2, adiponectin receptor 2; APPL1, DCC-interacting protein 13-alpha; CV, cardiovascular; OSA, obstructive sleep apnea; IR, ischemia/reperfusion; CABG, coronary artery bypass graft; n. d., not described.