Agonist-induced Piezo1 activation promote mitochondrial-dependent apoptosis in vascular smooth muscle cells
Qing Yin, Guangyao Zang, Nannan Li, Chenchen Sun, Rongzeng Du
Abstract
Abstract 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.