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The Role of Extracellular Vesicle-Derived miRNA in the Atherosclerotic Burden
Alessandra Stefania Rizzuto1, Isabella Fichtner2, Stefano Carugo3
1Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Milan, Italy.
Abstract:
In the context of atheroma-related sequelae, the role of extracellular vesicles (EVs) continues to spike interest. Their ability to traffic molecular cargo between cells highlights their role in intercellular communication, and consequently their involvement in mediating molecular events at the basis of physiological and pathologic processes. EVs encapsulate miRNAs within their lumen, shielding them from circulating ribonucleases, which would otherwise catalyze their degradation. However, there is an ongoing debate regarding the implication of miRNA contained within EVs in modulating biological activities on a molecular level. Therefore, the aim of the present review is to discuss the role of EV-derived miRNA, focusing on their implication in molecular mechanisms underlying atheroma formation. EVs of endothelial origin can regulate monocyte activation by transferring miR-10a that targets components of the inflammatory pathway. Tail vein administration of EVs derived from endothelial cells enriched in miR-34c-5p markedly reduces atherosclerosis progression. In patients with stable coronary artery disease, elevated levels of miR-126 and miR-199a in circulating EVs are significantly associated with a reduced incidence of major adverse cardiovascular event rate. These nanoparticles, released by all cells into most biological fluids, hold promise as a liquid biopsy tool as their circulating patterns and cargo can reflect the onset and severity of cardiovascular diseases.
Insights
Extracellular vesicles (EVs) carrying microRNAs (miRNAs) are key in cell communication and may influence atheroma formation. These EV-derived miRNAs show promise for diagnosing and treating cardiovascular diseases.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biotechnology
Background:
- Extracellular vesicles (EVs) mediate intercellular communication by transferring molecular cargo, including microRNAs (miRNAs).
- EV-encapsulated miRNAs are protected from degradation, but their role in modulating biological activities is debated.
- Atherosclerosis involves complex molecular events where EVs and their miRNA cargo may play a significant role.
Purpose of the Study:
- To review the role of EV-derived miRNAs in the molecular mechanisms of atheroma formation.
- To explore the potential of EV-derived miRNAs as biomarkers and therapeutic agents in cardiovascular diseases.
Main Methods:
- Literature review focusing on studies investigating EV-derived miRNAs in atherosclerosis.
- Analysis of experimental data on miRNA transfer by endothelial EVs and their impact on monocyte activation.
- Examination of clinical data correlating circulating EV-miRNA levels with cardiovascular event rates.
Main Results:
- Endothelial EVs transfer miR-10a, regulating monocyte activation via inflammatory pathways.
- EVs enriched with miR-34c-5p administration significantly reduced atherosclerosis progression in vivo.
- Elevated circulating EV levels of miR-126 and miR-199a correlate with reduced major adverse cardiovascular events in patients.
Conclusions:
- EV-derived miRNAs are implicated in the molecular pathogenesis of atherosclerosis.
- Circulating EV-miRNAs hold potential as sensitive biomarkers for cardiovascular disease risk and progression.
- EVs and their miRNA cargo represent a promising avenue for novel therapeutic strategies in cardiovascular medicine.
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