Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B

• DOI: 10.1111/bph.15826
• Publication Date: 2022-02-23T03:01:02Z
• Authors: Xianmei Pan; Rentao Wan; Yuman Wang; Silin Liu; Yu He; Bo Deng; Shangfei Luo; Yuan Chen; Lizhen Wen; Tianying Hong; Han Xu; Yifei Bian; Mingfeng Xia; Jing Li
• Keywords: Piezo1

Salvianolic acid B (SalB) is effective for treating cardiovascular diseases. However, the molecular mechanisms underlying its therapeutic effects remain unclear. Mechanosensitive Piezo1 channels play important roles in vascular biology, although their pharmacological properties are poorly defined. Here, we aimed to identify novel inhibitors and gain insights into of action.Intracellular Ca2+ ions were measured HUVECs, murine liver endothelial cells (MLECs), THP-1 RAW264.7 cell lines bone marrow-derived macrophages (BMDMs). Isometric tensions mouse thoracic aorta recorded. Shear-stress assays with HUVECs conducted. Patch-clamp recordings mechanical stimulation performed whole-cell mode. Foam formation was induced by BMDMs oxidised LDL (oxLDL). Atherosclerotic plaque Ldlr-/- genetically depleted mice on a high-fat diet.Salvianolic inhibited Yoda1-induced influx MLECs. Similar results observed macrophage BMDMs. Furthermore, demonstrated that salvianolic Yoda1- mechanically activated currents. suppressed aortic ring relaxation alignment direction shear stress. Additionally, Yoda1 enhanced foam cells, which reversed B. also atherosclerotic plaques insensitive genetic depletion.Our study provides mechanistic inhibitory role against improves our understanding preventing lesions.