Oxidized phospholipid POVPC contributes to vascular calcification by triggering ferroptosis of vascular smooth muscle cells

• DOI: 10.1096/fj.202302570r
• Publication Date: 2024-04-06T08:55:28Z
• Authors: Lihe Lu; Yuanzhi Ye; Yajun Chen; Liyun Feng; Jiali Huang; Qingchun Liang; Zirong Lan; Qianqian Dong; Xiaoyu Liu; Yining Li; Xiuli Zhang; Jing‐Song Ou; An Chen; Jianyun Yan
• Keywords: 0301 basic medicine; Cyclohexylamines; Phosphorylcholine; Myocytes, Smooth Muscle; Phenylenediamines; Muscle, Smooth, Vascular; 03 medical and health sciences; Osteogenesis; Humans; Ferroptosis; Reactive Oxygen Species; Vascular Calcification; Phospholipids; Cells, Cultured

Abstract Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1‐Palmitoyl‐2‐(5′‐oxo‐valeroyl)‐sn‐glycero‐3‐phosphocholine (POVPC), oxidized phospholipid, found atherosclerotic plaques has been shown to induce oxidative stress. However, the effects POVPC on VSMCs have yet be studied. In present study, we investigated using vitro ex vivo models. increased mineralization arterial rings, as by alizarin red staining. addition, treatment expression markers Runx2 BMP2, indicating that promotes transition VSMCs. Moreover, stress impaired mitochondria function VSMCs, ROS levels, impairment mitochondrial membrane potential, decreased ATP levels. Notably, ferroptosis triggered was confirmed levels intracellular ROS, lipid MDA, which were ferrostatin‐1, inhibitor. Furthermore, ferrostatin‐1 attenuated POVPC‐induced Taken together, our study for first time demonstrates via activation VSMC ferroptosis. Reducing or inhibiting might provide novel strategy treat calcification.