Extracellular-vesicle containing miRNA-503-5p released by macrophages contributes to atherosclerosis

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Biology

Background:

• Atherosclerosis involves endothelial dysfunction and smooth muscle cell (SMC) differentiation.
• Macrophages within atherosclerotic plaques drive inflammation and interact with SMCs.
• Extracellular vesicles (EVs) play a role in intercellular communication.

Purpose of the Study:

• To investigate the role of microRNA-503-5p (miR-503-5p) in atherosclerosis.
• To elucidate the mechanism of miR-503-5p transfer and its effects on endothelial cells and SMCs.
• To evaluate miR-503-5p as a potential therapeutic target for atherosclerosis.

Main Methods:

• Quantification of miR-503-5p in EVs from macrophages and patient samples.
• Co-culture experiments with human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs).
• Analysis of cell proliferation, migration, and angiogenesis.
• Western blot analysis of Smad family members.
• In vivo studies using atherosclerotic mouse models with lentiviral inhibition of miR-503-5p.

Main Results:

• miR-503-5p was enriched in EVs from macrophages and atherosclerosis patients.
• EV-mediated transfer of miR-503-5p reduced HCAEC function and enhanced HCASMC proliferation/migration.
• miR-503-5p negatively regulated Smad family members 1, 2, and 7.
• miR-503-5p enhanced inflammatory cytokines and adhesion molecules via Smad down-regulation.
• Inhibition of miR-503-5p reduced atherosclerotic lesion formation in mice.

Conclusions:

• A novel mechanism of intercellular communication involving miR-503-5p and EVs in atherosclerosis was identified.
• miR-503-5p promotes atherosclerosis by modulating endothelial and smooth muscle cell behavior.
• miR-503-5p represents a potential therapeutic target for atherosclerosis treatment.