Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu Province, China.
School of Medicine, Jiangsu University, Zhenjiang, 212001, Jiangsu Province, China.
BMC Cardiovasc Disord. 2022 Jun 24;22(1):287. doi: 10.1186/s12872-022-02726-2.
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.
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 were assessed via fluorescence microscope, and the mitochondrial transmembrane potential was monitored by JC-10 staining.
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 overload, mitochondrial damage, accumulation of ROS, and VSMCs apoptosis in a dose-depend manner. Furthermore, BAPT-AM (an intracellular Ca chelator) and NAC (an antioxidant) suppressed the mitochondrial damage and attenuated the VSMCs apoptosis.
Our study suggested that Piezo1 induced VSMCs apoptosis because of Ca overload, excessive ROS generation, and mitochondrial dysfunction, which indicated that Piezo1 has potential value in treating vascular diseases.
机械损伤在动脉粥样硬化的进展中起着至关重要的作用。Piezo1 是一种新型的机械敏感离子通道。本研究探讨了 Piezo1 激活诱导的血管平滑肌细胞（VSMCs）凋亡及其潜在机制。
我们分别通过细胞计数试剂盒-8（CCK-8）和 Annexin V-FITC/PI 流式细胞术检测细胞活力和凋亡率。然后通过 Western blot 测量相对蛋白。通过荧光显微镜评估活性氧（ROS）和细胞内 Ca，通过 JC-10 染色监测线粒体跨膜电位。
我们的体外研究表明，与对照组相比，ApoE-/-组小鼠的 Piezo1 表达更高（P<0.05）。此外，Piezo1 激动剂 Yoda1 以剂量依赖的方式引发 Ca 超载、线粒体损伤、ROS 积累和 VSMCs 凋亡。此外，BAPT-AM（细胞内 Ca 螯合剂）和 NAC（抗氧化剂）抑制了线粒体损伤并减轻了 VSMCs 凋亡。
我们的研究表明，Piezo1 通过 Ca 超载、过多的 ROS 生成和线粒体功能障碍诱导 VSMCs 凋亡，这表明 Piezo1 在治疗血管疾病方面具有潜在价值。
