Emerging Role of Macrophage-Fibroblast Interactions in Cardiac Homeostasis and Remodeling
Xuzhe Zhang, Qin-Lin Li, Tingting Tang, Xiang Cheng
Abstract
• Interactions between cardiac macrophages and fibroblasts significantly affect cardiac homeostasis and remodeling, offering potential therapeutic targets of heart failure. • This review presents the current evidence regarding the heterogeneity and plasticity of cardiac macrophages and fibroblasts, elucidates the diverse molecular mechanisms potentially governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, and assesses the key mediators involved from a translational perspective. • Despite advances in basic research, translating experimental findings into effective clinical treatment strategies remains challenging. We emphasize that interventions targeting cardiac macrophage-fibroblast interactions should be based on understanding their dynamics across the pathophysiologic spectrum of cardiac homeostasis and remodeling. As major noncardiomyocyte components in cardiac tissues, macrophages and fibroblasts play crucial roles in maintaining cardiac homeostasis, orchestrating reparative responses after cardiac injuries, facilitating adaptive cardiac remodeling, and contributing to adverse cardiac remodeling, owing to their inherent heterogeneity and plasticity. Recent advances in research methods have yielded novel insights into the intricate interactions between macrophages and fibroblasts in the cardiac context. This review aims to comprehensively examine the molecular mechanisms governing macrophage-fibroblast interactions in cardiac homeostasis and remodeling, emphasize recent advancements in the field, and offer an evaluation from a translational standpoint.