Novel therapeutic targets for atherosclerosis: Targeting the FOSB-MECP2-Commd1 pathway.

Abstract

Atherosclerosis (AS) is a systemic disease and represents the primary underlying pathology of cardiovascular diseases. In this study, we aim to elucidate the roles of FBJ osteosarcoma oncogene B (FOSB) in AS development. ApoE^-/- mice were used and fed a high-fat diet to establish an AS model. We observed elevated expression of FOSB in aortic tissues, which was associated with increased lipid deposition, macrophage recruitment. Knockdown of FOSB mitigated these AS-related pathological changes, and decreased the levels of TNF-α, IL-6 and IL-1β in aortic tissues and ox-LDL-induced RAW264.7 cells. Further investigations revealed that FOSB enhances the transcriptional activity of MECP2 by binding to its promoter region. MECP2 was found to be upregulated in aortic tissues and ox-LDL-induced RAW264.7 cells, exacerbating ox-LDL-induced cellular damage. Additionally, our study identifies Commd1 as a downstream target of MECP2. Overexpression of Commd1 reduced levels of TNF-α and IL-6, alleviating ox-LDL-induced inflammation and lipid deposition. In summary, our findings unveil a complex molecular interplay involving FOSB, MECP2, and Commd1 in AS pathogenesis. This study not only enhances our understanding of AS molecular mechanisms but also proposes potential therapeutic targets for its treatment.