Agonist-induced Piezo1 activation promote mitochondrial-dependent apoptosis in vascular smooth muscle cells

OBJECTIVE: Mechanical damage plays an essential role in the progression of atherosclerosis. Piezo1 is a new mechanically sensitive ion channel. The present study investigated the vascular smooth muscle cells (VSMCs) apoptosis induced by Piezo1 activation and explored its underlying mechanism. METHODS: We evaluated cell viability and apoptosis rate with cell counting kit-8 (CCK-8) and Annexin V-FITC/PI flow cytometry assay, respectively. And then Western blot was performed to measure the relative protein. Reactive oxygen species (ROS) and intracellular Ca(2+) were assessed via fluorescence microscope, and the mitochondrial transmembrane potential was monitored by JC-10 staining. RESULTS: Our in vitro study revealed that mice in the ApoE-/- group compared with control mice showed higher Piezo1 expression(P < 0.05). Besides, Yoda1, a Piezo1 agonist, triggered Ca(2+) overload, mitochondrial damage, accumulation of ROS, and VSMCs apoptosis in a dose-depend manner. Furthermore, BAPT-AM (an intracellular Ca(2+) chelator) and NAC (an antioxidant) suppressed the mitochondrial damage and attenuated the VSMCs apoptosis. CONCLUSION: Our study suggested that Piezo1 induced VSMCs apoptosis because of Ca(2+) overload, excessive ROS generation, and mitochondrial dysfunction, which indicated that Piezo1 has potential value in treating vascular diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-02726-2.