Macrophage-Specific SPP1 Contributes to Pressure Overload-Induced Cardiac Dysfunction and Maladaptive Remodeling - PubMed
4 hours ago
- #SPP1
- #cardiac remodeling
- #macrophage
- SPP1-expressing macrophages are a pathogenic subset that emerges early after pressure overload induced by transverse aortic constriction.
- Deleting Spp1 in myeloid cells reduced inflammation, pathological remodeling, and cardiac dysfunction.
- Stressed cardiomyocytes release HMGB1, activating NLRP3 inflammasome in macrophages and leading to SPP1 production via NF-κB p65.
- Targeting the HMGB1-NLRP3-SPP1 axis with arglabin (an NLRP3 inhibitor) suppressed SPP1 expression, reduced immune cell infiltration and fibrosis, and alleviated adverse remodeling.
- The HMGB1-NLRP3-NF-κB-SPP1 axis in macrophages is critical for pressure overload-induced cardiac pathogenesis and represents a promising therapeutic target.