Figure 5.

A schematic illustration of the mechanism of P2X7R in pressure overload-induced cardiac fibrosis and TGF-β1-induced CF activation. In TAC-induced injury, pathological stress, such as pressure overload and TGF-β1, triggers the release of ATP. Elevated ATP activates P2X7 receptors, contributing to P2X7-mediated NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activation. This induces the release of IL-1β, causing severe inflammation that precipitates cardiac fibrosis and aggravates TGF-β1-induced CF activation. Moreover, inhibition of P2X7R with BBG inhibitor in TAC mice or CFs primed with TGF-β1 reduces fibrotic extracellular matrix (ECM) gene expression and cardiac fibrosis.