Fig. 7

Graphical abstract. The proposed mechanism by which ATX inhibition regulates the pathological development of FCAVD is illustrated in the schematic diagram. In diseased valves, an inflammatory environment emerges, causing immune cells such as macrophages to infiltrate the valvular tissue and release inflammatory cytokines (e.g., IL-1β). ① This IL-1β upregulates the expression of LPAR1, which strengthens the action of ATX-LPA. In addition, Lp(a) carrying ATX and LPC accumulates in the valves, while activated VICs secrete additional ATX [12, 31]. ② ATX subsequently converts LPC into LPA, which binds to the increased LPA receptor (LPAR), activating the TGF-β signaling pathway [32]. ③ In turn, this activation promotes fibro-calcific remodeling by inducing the expression of CTGF and IL-6 via the TGF-β signaling axis. Importantly, ATX inhibition specifically hinders the activation of ATX-LPA enhancing TGF-β-linked signaling and ultimately alleviating fibrosis and calcium deposition in the activated VICs