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Inhibition of miR-33 reduces atherosclerotic plaque burden, but miR-33 deficient mice are predisposed to the development of obesity and metabolic dysfunction. The proatherogenic effects of miR-33 are thought to be in large part because of its repression of macrophage cholesterol efflux, through targeting of Abca1 (ATP-binding cassette subfamily A member 1). However, targeting of other factors may also be required for the beneficial effects of miR-33, and currently available approaches have not allowed researchers to determine the specific impact of individual miRNA target interactions in vivo.

In this work, we sought to determine how specific disruption of Abca1 targeting by miR-33 impacts macrophage cholesterol efflux and atherosclerotic plaque formation in vivo.

We have generated a novel mouse model with specific point mutations in the miR-33 binding sites of …