Targeting the CCND1-PDK4 Axis to Promote Reparative Macrophage Phenotype and Mitigate Post-Myocardial Infarction Cardiac Remodeling

Highlight

• CCND1 expression decreases in monocytes and cardiac macrophages after myocardial infarction (MI), correlating with adverse cardiac remodeling.
• Macrophage-specific deletion of CCND1 exacerbates inflammation and worsens cardiac dysfunction following MI.
• CCND1 interacts with PDK4, facilitating its ubiquitination via RPL11 and MDM2, suppressing PDK4’s phosphorylation of PDH, thereby enhancing glucose oxidation in macrophages.
• Therapeutic targeting of the CCND1-PDK4 axis in macrophages promotes reparative phenotype transition, improving cardiac function post-MI independently of CCND1’s cell cycle role.

Study Background