Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target
Abstract
:1. Introduction
2. Overview of Exosomes
3. The Link between Cardiovascular Disease and Exosomes
3.1. Exosome Cargo and the Cardiovascular System
3.2. Exosomes in Atherosclerosis: Endothelial Dysfunction, Macrophage Recruitment, and Vascular Smooth Muscle Behavior
3.3. Exosomes in Apoptosis
3.4. Exosomes in Hypertrophy
3.5. Exosomes in Angiogenesis
3.6. Exosomes in Cardiac Fibrosis
3.7. Exosomes in Myocardial Infarction
3.8. Adipose Tissue Exosomes
Cell/Tissue Source of Exosomes | Reference | CVD Impact | Key Cargo Involved |
---|---|---|---|
Carotid atherosclerotic tissue | [36] | Endothelial inflammation in rats | Whole exosomes |
Endothelial progenitor cells (EPC) | [44] | ↓ oxidative stress and inflammation and ↓ plaque area in hyperglycemic mouse model | Whole exosomes |
Cardiomyocyte | [49] | Protects against apoptosis, remodeling and cardiac hypertrophy in diabetic mice | Heat shock protein (HSP)-20, |
Cardiomyocyte | [50,51] | Atherogenic via induction of inflammatory mediators | HSP-60 |
Blood | [56,57] | Anti-inflammatory, atheroprotective effects on macrophages via IL-10 release, facilitation of cholesterol efflux | HSP-27 |
Blood | [59] | Delivery of free fatty acids to cardiac endothelium and myocytes for energy | CD36 |
Arterial endothelium | [64,65] | Monocyte activation and adhesion | HSP-70 |
Macrophage foam cells | [71,72] | Enhanced adhesion and suppressed apoptosis of vascular smooth muscle cells | MiR-186-5p |
Cardiac fibroblasts | [77,78,79] | ↓ infarct size in rat ischemia-reperfusion injury, limited apoptosis | MiR-423-3p |
Human mesenchymal stem cells | [88] | ↓ cardiac markers for cardiomyocyte hypertrophy and ↓ inflammatory cytokine levels | Whole exosomes |
Human cardiospheres | [89] | ↓ left ventricular fibrosis and hypertrophy in a mouse cardiac hypertrophy model | MiRNA-148a |
Human adipose tissue mesenchymal stem cells | [91] | Promote angiogenesis | MiR-125a |
Cardiomyocyte after hypoxic preconditioning | [92,93] | Promote angiogenesis and protect microvascular endothelium from oxidative damage | MiR-222 and miR-143 |
Primary neonatal cardiomyocytes | [94,95] | Anti-angiogenic | MiR-19a-3p |
Blood | [97,98,99] | ↑ proliferation, migration and tube-formation in endothelial cells | MiR-126 and miR-199a |
Inflammatory M1 macrophages | [101,102] | Anti-angiogenic | MiR-155 |
Heart after exercise | [109] | ↓ fibrosis | MiR-29b and miR-455 |
Cardiomyocyte | [111] | ↑ fibrosis and hypertrophy | MiR-217 |
Cardiomyocytes after mechanical stress | [112] | ↓ fibrosis | MiR-378 |
Cardiomyocytes after mechanical stress | [113] | ↑ fibrosis | MiR-494-3p |
Perivascular adipose tissue | [126] | Atheroprotective, ↑ macrophage cholesterol efflux, ABCA1, and ABCG1 | MiR-382-5p |
Obese mouse adipose tissue macrophages | [131] | Confer insulin resistance on lean mice | Whole exosomes |
4. Exosomal MiRNAs of Specific Interest in CVD
4.1. MiR-19b
4.2. MiR-130a
4.3. MiR-10b
4.4. MiR-33
4.5. MiR-186-5p
MiRNA | Reference | Model Where Studied | Effect on the Cardiovascular System |
---|---|---|---|
MiR-19b | [137,138] | Elevated in persons with angina, further investigated in mice | ↑atherosclerosis with ↑ lipids, ↑vascular smooth muscle, ↑ apoptosis |
MiR-130a | [142,143] | Inverse association with coronary disease in humans, further investigated in mice and cultured human endothelial cells | Stimulates ↑ in serum levels of inflammatory cytokines |
MiR-10b | [146,147,148,149,150] | Elevated level in plasma and in arteries in humans with atherosclerosis, further investigated in mice and cultured human endothelial cells and both mouse and human macrophages | Associated with pro-stenotic endothelial cell phenotype. Downregulates cholesterol efflux proteins ABCA1 and ABCG1 in macrophages. |
MiR-33 | [161,162,163,164,165,166] | Mice, rats and primates. | Potent inhibitor of ABCA1. Knockdown of miR33 in animal models increases HDL and enhances cholesterol efflux. |
MiR-186-5p | [167] | Elevated in persons following acute myocardial infarction, further investigated in cell culture and mice | ↓ levels in exosomes after myocardial infarction. Cultured macrophages exposed to these exosomes show ↑ scavenger receptor expression and ↑ cholesterol uptake |
5. Leveraging Exosomes for CVD Treatment
6. Exosome Delivery for Therapeutic Applications
7. Exosomes and miRNAs as Biomarkers of CVD
8. Challenges in the Application of Exosomes in Diagnosis and Treatment
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Reiss, A.B.; Ahmed, S.; Johnson, M.; Saeedullah, U.; De Leon, J. Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target. Metabolites 2023, 13, 479. https://doi.org/10.3390/metabo13040479
Reiss AB, Ahmed S, Johnson M, Saeedullah U, De Leon J. Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target. Metabolites. 2023; 13(4):479. https://doi.org/10.3390/metabo13040479
Chicago/Turabian StyleReiss, Allison B., Saba Ahmed, Maryann Johnson, Usman Saeedullah, and Joshua De Leon. 2023. "Exosomes in Cardiovascular Disease: From Mechanism to Therapeutic Target" Metabolites 13, no. 4: 479. https://doi.org/10.3390/metabo13040479