fig4

Figure 4. Schematic illustration of macrophage mechanotransduction in response to elevated extracellular matrix (ECM) stiffness during cardiac fibrosis. Macrophages sense elevated ECM stiffness through diverse mechanosensitive elements, including integrins, Piezo1 mechanosensitive ion channels, Notch receptors, and the YAP/TAZ transcription module. These mechanical inputs are transduced via cytoskeletal remodeling and downstream signaling including YAP/TAZ activation, leading to transcriptional reprogramming of pro-fibrotic and inflammatory genes. Piezo1-mediated Ca²⁺ influx further amplifies CCR2 and Notch signaling, coordinating macrophage recruitment, polarization, and effector functions. Together, these mechano-adaptive responses contribute to cardiac fibrosis by promoting cytokine production, migration, and fibroblast activation.