Mechanical stress accelerates vascular calcification by Piezo1/BMP2 of vascular smooth muscle cells.

Hemodialysis is the main renal replacement therapy for end-stage renal disease. Blood vessels are susceptible to vascular calcification (VC) in patients with maintenance hemodialysis, which is linked to mortality. Arteriovenous fistulas as frequently used hemodialysis access suffer from mechanical stress, often developing VC, which impairs hemodialysis quality. Piezo1, as a mechanosensitive ion channel receptor in vascular smooth muscle cells (VSMCs), is essential for the sensing and transduction of mechanical stress. However, whether and how mechanical stress accelerates VC by Piezo1 is unclear. Here we observed, Radial arteries with VC from patients with maintenance hemodialysis showed higher Piezo1 expression. In vitro, VSMCs under high phosphorus or high hydrostatic pressure (HP) showed more expression of Piezo1, and calcification, including higher calcium deposition and osteogenic differentiation. Activating Piezo1 by Yoda1 showed significant calcification. Inhibition of Piezo1 by GsMTx4 or silence of Piezo1 inhibited HP-induced calcification. Similar results were obtained from rat aortas in vitro. Inhibition of BMP2 by Noggin alleviated HP-induced or Yoda1-induced calcification. Endoplasmic reticulum stress and calcium ion influx were activated in VSMCs under HP by Piezo1. Collectively, our results suggest mechanical stress accelerates VC by Piezo1/BMP2 of VSMCs.