Abstract 13: Macrophage Erk5 Activation Induced by Apoptotic Cells and Statins Promotes Efferocytosis and Inhibits Atherosclerosis Formation

BackgroundsDefective efferocytosis (phagocytic clearance of dying cells) is critically linked to progression of advanced atherosclerotic lesions. Although it has been well known that efferocytosis is processed by molecules including eat-me and find-me signals, it is unclear how efferocytosis becomes defective in advanced lesion. Methods and ResultsHere, we found that bone marrow-derived macrophages (BMDM) from macrophage-specific ERK5 knockout (ERK5fl/flLysMCre+/-; ERK5-MKO) mice reduced mRNA and proteins levels of efferocytosis-related signaling molecules such as Mer-tK, C1qa, C1qb, C1qc, Gas6, Mfg-e8, Thbs1, and Anxa1 compared with BMDM from non-transgenic control (NLC) mice. Interestingly, addition of apoptotic cells and pitavastatin activate ERK5 kinase activity and increase opsonins, eat-me and find-me signals, and phagocytic capacity toward apoptotic cells in normal macrophage, but macrophages from ERK5-MKO failed to respond in this manner. ERK5-MKO crossed to LDLR-/- mice and fed a high cholesterol...