Abstract 15966: Macrophage P90rsk Accelerates Atherosclerosis by Inhibiting Efferocytosis

Backgrounds: We have previously reported that ERK5 activation promotes efferocytosis and downregulates atherosclerosis (AS). The impairment of efferocytosis in advanced plaque has been suggested, but the regulatory mechanisms are largely unknown. Methods and Results: Immunohistochemistry studies on LDLR-/- mice showed that p90RSK activation was significantly up-regulated in advanced plaques, especially in MΦ. We have reported that p90RSK activation inhibits ERK5 transcriptional activity and intensifies endothelial inflammation via phosphorylation of ERK5 S496. In this study, we investigated the role of MΦ p90RSK in regulating ERK5 and efferocytosis. Angiotensin II (AngII) is known to impair efferocytosis and we found that 200 nM AngII activated p90RSK. AngII treatment and adenovirus (Ad)-wild type (WT) p90RSK overexpression inhibited ERK5 transcriptional activity and subsequent expression of the efferocytosis- and M2-type-related genes. These inhibitions were completely reversed by a highly selective p90R...