MicroRNA-202-5p-dependent inhibition of Bcl-2 contributes to macrophage apoptosis and atherosclerotic plaque formation.

BACKGROUND

The identification of microRNA (miRNA)-related molecular mechanisms has advanced the development of new therapeutics for atherosclerosis (AS). The roles of miR-202-5p- in the pathogenic mechanisms of AS have not been explored.

METHODS

Macrophages were transfected with a series of miR-202-5p mimic/inhibitor, and then assessed for changes in viability, apoptosis, and secretion of inflammatory cytokines. The regulatory mechanism of miR-202-5p was explored through dual-luciferase reporter gene assay. A mouse model of AS was developed in ApoE mice fed with high-fat diet to examine the in vivo effects of miR-202-5p on atherosclerotic plaque formation, collagen synthesis, and fiber cap thickness.

RESULTS

Elevated miR-202-5p was found in atherosclerotic plaque tissues of the mice. miR-202-5p was able to induce macrophage apoptosis and release of pro-inflammatory factors. Besides, miR-202-5p limited Bcl-2 expression and elevated the levels of Bax, cleaved caspase-3, and cleaved caspase-9. Bcl-2 was concluded as a target gene of miR-202-5p. The pro-apoptotic effect of miR-202-5p on macrophages was achieved via limiting Bcl-2. In the mouse AS model, restoration of miR-202-5p stimulated atherosclerotic plaque formation, but reduced collagen synthesis and fiber cap thickness.

CONCLUSION

These data collectively suggest a pro-apoptotic action of miR-202-5p in macrophages that contributes to atherosclerotic plaque formation.