Proefferocytic Therapy Promotes Transforming Growth Factor-β Signaling and Prevents Aneurysm Formation
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“Efferocytosis” (Greek: to carry the dead to the grave) is the term used to describe the phagocytic removal of apoptotic cells. Impaired efferocytosis was recently shown to be causal for atherosclerosis, where an imbalance in so-called eat me ligands allows uncleared cells to accumulate in the plaque and potentiate lesion expansion. We showed that this defect could be reversed with proefferocytic therapies, which led to marked reductions in disease burden.1 The majority of the antiatherosclerotic benefit appeared to occur via specific targeting of apoptotic debris and regression of the necrotic core.2
It is important to note, however, that the consequences of efferocytic signaling extend beyond the simple engulfment of diseased cells. For example, macrophages that have successfully phagocytosed an apoptotic body are known to secrete a number of antiinflammatory factors.3 Some of these could theoretically influence vessel integrity, medial degeneration, and macrophage recruitment. Accordingly, we hypothesized that efferocytosis could have relevance to vascular disorders other than atherosclerosis, including those not driven by growth of the necrotic core, such as abdominal aortic aneurysm (AAA). Ethics and Institutional Review Board approvals were provided by Stanford University (protocol 27279), the Karolinska Institute (protocols N48/16 and N30/16), and the Munich …