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

Area of Science:

• Cardiovascular Biology
• Molecular Pathology
• Oncology

Background:

• Atherosclerosis (AS) is a systemic disease and the primary cause of cardiovascular diseases.
• Understanding the molecular mechanisms driving AS is crucial for developing effective treatments.

Purpose of the Study:

• To elucidate the role of FBJ osteosarcoma oncogene B (FOSB) in the development of atherosclerosis.
• To investigate the molecular pathway involving FOSB, MECP2, and Commd1 in AS pathogenesis.

Main Methods:

• Atherosclerosis model in ApoE-/- mice fed a high-fat diet.
• Analysis of FOSB expression and its association with lipid deposition and macrophage recruitment.
• Investigating the interaction between FOSB and MECP2, and MECP2's regulation of Commd1.
• Assessing the impact of FOSB, MECP2, and Commd1 modulation on inflammatory markers (TNF-α, IL-6, IL-1β) and lipid deposition in vitro and in vivo.

Main Results:

• Elevated FOSB expression in atherosclerotic aortic tissues correlated with increased lipid deposition and macrophage infiltration.
• FOSB knockdown reduced AS pathology and inflammatory cytokine levels.
• FOSB enhances MECP2 transcriptional activity, leading to MECP2 upregulation and exacerbation of ox-LDL-induced cellular damage.
• Commd1, a downstream target of MECP2, was found to alleviate ox-LDL-induced inflammation and lipid deposition upon overexpression.

Conclusions:

• FOSB, MECP2, and Commd1 form a critical molecular axis in atherosclerosis pathogenesis.
• This pathway contributes to inflammation and lipid accumulation in AS.
• The identified FOSB-MECP2-Commd1 axis presents potential therapeutic targets for atherosclerosis treatment.