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The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis
Kai-Uwe Jarr 1, Jianqin Ye 1, Yoko Kojima 1, Zhongde Ye 1, Hua Gao 1, Sofie Schmid 2, Lingfeng Luo 1, Richard A Baylis 1, Mozhgan Lotfi 1, Nicolas Lopez 1, Anne V Eberhard 1, Bryan Ronain Smith 3 4, Irving L Weissman 5, Lars Maegdefessel 2 6 7, Nicholas J Leeper 1 8 9
...In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NFκB1 p50 and suppressing the expression of the critical 'don't eat me' molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47-SIRPα blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of pro-phagocytic therapies independently of any lipid-lowering effect.