CCND1 Mitigates Ischemia-Induced Pathological Cardiac Remodeling by Promoting Cardiac Monocyte-Derived Macrophage Transition to a Reparative Phenotype.

CCND1 is significantly decreased in peripheral blood mononuclear cells, monocytes, and cardiac macrophages after myocardial infarction, and its loss worsens post-MI cardiac dysfunction and adverse remodeling in mice.

• Why it matters: Inflammation resolution and reparative reprogramming after MI depend on how recruited monocyte-derived macrophages are instructed, but the controlling molecular pathway is not well defined.
• What they did: Human samples were profiled by single-cell RNA sequencing, and mouse monocyte-derived macrophage behavior after MI was tested with lineage tracing, transplantation, metabolite profiling, and macrophage-specific Ccnd1 knockout; CCND1–PDK4 interactions were examined via ubiquitination assays.
• The result: CCND1 directly interacted with PDK4, promoting its ubiquitination via RPL11 and mouse double minute 2, which suppressed PDH phosphorylation, increased glucose oxidation, and shifted macrophages toward an anti-inflammatory phenotype; CCND1 motif overexpression or PDK4 knockdown improved cardiac function and remodeling after MI.

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