Heart failure & cardiomyopathies
CCND1 Mitigates Ischemia-Induced Pathological Cardiac Remodeling by Promoting Cardiac Monocyte–Derived Macrophage Transition to a Reparative Phenotype
Authors' conclusion
Our findings identify the CCND1-PDK4 axis as a key regulator of macrophage functional reprogramming toward a reparative phenotype after MI
Study context
- Population
- Patients with and without myocardial infarction (MI) (peripheral blood mononuclear cells); mouse MI model
Methodological detailshuman single-cell RNA sequencing, genetic lineage tracing, macrophage-specific Ccnd1 knockout mice, MI mouse model
- Human single-cell RNA sequencing
- Genetic lineage tracing
- Macrophage-specific Ccnd1 knockout mice
- MI mouse model
Main finding
As reported in the abstract
- CCND1 levels in PBMCs, monocytes and cardiac macrophages from MI patients significantly decreased
- Macrophage-specific and monocyte-derived macrophage-specific CCND1 deletion worsened MI-induced cardiac dysfunction and adverse remodeling, via amplified inflammatory responses
- CCND1 directly interacted with PDK4 and facilitated its ubiquitination by recruiting RPL11 and mouse double minute 2
- CCND1 suppressed PDK4-driven PDH phosphorylation, enhanced glucose oxidation and shifted macrophages toward an anti-inflammatory phenotype
- Overexpression of the CCND1-PDK4 binding motif or PDK4 knockdown in macrophages improved cardiac function and mitigated adverse remodeling after MI, independent of CCND1's cell cycle role
Original publication
CCND1 Mitigates Ischemia-Induced Pathological Cardiac Remodeling by Promoting Cardiac Monocyte–Derived Macrophage Transition to a Reparative Phenotype. Circulation. Published 15 September 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →