The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis.

Autor: Jarr KU; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Ye J; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Kojima Y; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Ye Z; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Gao H; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Schmid S; Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany., Luo L; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Baylis RA; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Lotfi M; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Lopez N; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Eberhard AV; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America., Smith BR; Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan, United States of America.; Institute for Quantitative Health Science and Engineering, East Lansing, Michigan, United States of America., Weissman IL; Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, United States of America., Maegdefessel L; Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.; German Center for Cardiovascular Research, Berlin, Germany (DZHK partner site Munich Heart Alliance).; Department of Medicine, Karolinska Institute, Stockholm, Sweden., Leeper NJ; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, California, United States of America.; Stanford Cardiovascular Institute, Stanford University, Stanford, California, United States of America.; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2022 Mar; Vol. 1 (3), pp. 253-262. Date of Electronic Publication: 2022 Mar 07.
DOI: 10.1038/s44161-022-00023-x
Abstrakt: The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPα inhibition identifies a link between statins, efferocytosis, and vascular inflammation. 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.
Competing Interests: Competing Interests I.L.W. and N.J.L. are co-founders and directors of Bitterroot Bio Incorporated, a cardiovascular company studying macrophage checkpoint inhibition. K.-U.J., Y.K., I.L.W., and N.J.L. have filed a provisional patent (U.S. Application Serial No. 63/106,794): ‘CD47 Blockade and Combination Therapies Thereof For Reduction Of Vascular Inflammation’. The remaining authors declare no competing interests.
Databáze: MEDLINE
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