Heart failure & cardiomyopathies
CD206 + IL-4Rα + Macrophages Are Drivers of Adverse Cardiac Remodeling in Ischemic Cardiomyopathy
Authors' conclusion
Cardiac CD206+IL-4Rα+ macrophages proliferate and expand in HF and are key mediators of pathological remodeling and fibrosis, in part through the secretion of FIZZ1.
Study context
- Population
- Adult C57BL/6 mice with heart failure (HF) after nonreperfused MI; human failing hearts
Main finding
As reported in the abstract
- CD206+ macrophages steadily expanded in hearts after MI, comprising ≈85% of all macrophages at 8 weeks; proliferative, mostly CCR2- and MHC IIhi, correlated with left ventricular (LV) dysfunction and fibrosis
- Nearly half of CD206+ macrophages expressed IL-4Rα; majority of CD206+IL-4Rα+ macrophages coexpressed profibrotic FIZZ1
- M[IL-4] macrophages upregulated FIZZ1 and induced FIZZ1-dependent myofibroblast differentiation of cardiac mesenchymal stem cells and fibroblasts, partly via DLL-4/Jagged1-Notch1 signalling
- Intramyocardial transfer of M[IL-4], but not M[IL-10], CD206+ macrophages to naïve mice induced progressive LV remodeling over 4 weeks (more fibrosis, cardiomyocyte hypertrophy, apoptosis)
- Myeloid-specific IL-4Rα deletion in HF (from 4 weeks after MI) reduced CD206+ macrophage proliferation, depleted CD206+IL-4Rα+ macrophages, abrogated LV remodeling progression, reduced fibrosis, improved neovascularization
- In vivo IL-4Rα silencing in established HF depleted CD206+IL-4Rα+ macrophages, reversed LV remodeling (improved fibrosis, neovascularization, dysfunction) and suppressed local and systemic inflammation
- CD206+ and CD163+ macrophages significantly expanded in human failing hearts and correlated with fibrosis; most CD163+ macrophages expressed IL-4Rα and FIZZ3
Original publication
CD206 + IL-4Rα + Macrophages Are Drivers of Adverse Cardiac Remodeling in Ischemic Cardiomyopathy. Circulation. Published 1 May 2025. doi:10.
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