M1 macrophages-derived extracellular vesicles elevate microRNA-185-3p to aggravate the development of atherosclerosis in ApoE mice by inhibiting small mothers against decapentaplegic 7.

OBJECTIVE

Extracellular vesicles (EVs) are vital mediators of transferring microRNAs (miRNAs). We focused on effect of miR-185-3p that mediated by macrophages-derived EVs on atherosclerosis (AS) by targeting small mothers against decapentaplegic 7 (Smad7).

METHODS

EVs were extracted from M1 macrophages and identified. ApoE mice were treated with EVs, EVs containing miR-185-3p inhibitor or mimic, then the pathological changes of mouse aorta were observed. The levels of blood lipid, cell adhesion molecules, oxidative stress factors, inflammatory factors, and proliferation and apoptosis of vascular endothelial cells were assessed. Expression of miR-185-3p and Smad7 was detected and the targeting relationship between miR-185-3p and Smad7 was validated.

RESULTS

MiR-185-3p was upregulated while Smad7 was downregulated in atherosclerotic mouse aorta. M1 macrophages-derived EVs elevated miR-185-3p to promote development of AS pathology and levels of blood lipid, endothelial cellular adhesion, oxidative stress factors and inflammatory factors, suppressed cell proliferation and promoted cell apoptosis of vascular endothelial cells in atherosclerotic mice through downregulating Smad7. Smad7 was a target gene of miR-185-3p and miR-185-3p could inhibit expression of Smad7.

CONCLUSION

M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE mice by negatively regulating Smad7. This research may further the understanding of AS mechanism.