Piezo1 in endothelial cells is involved in vitamin D-induced vascular calcification

Area of Science:

• Cardiovascular Biology
• Mechanobiology
• Endothelial Cell Function

Background:

• Vascular calcification is a significant risk factor for cardiovascular disease.
• The role of the Piezo1 channel in vascular endothelial cells regarding vascular calcification remains unclear.

Purpose of the Study:

• To investigate the involvement of the Piezo1 channel in endothelial cells in the pathogenesis of vascular calcification.
• To explore the effects of Piezo1 activation and inhibition on vascular calcification markers.

Main Methods:

• Induction of hypercalcemia and vascular calcification in mice using vitamin D injection.
• Administration of Piezo1 channel antagonist (GsMTx4) and agonist (Yoda1).
• Assessment of aortic calcium content, vascular tension, pulse wave velocity, endothelial cell function (NO production, eNOS expression), and gene expression in co-cultured human umbilical vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs).

Main Results:

• Vitamin D administration increased serum calcium, aortic calcium content, vascular tension, and pulse wave velocity.
• GsMTx4 treatment alleviated arteriosclerosis and reduced aortic calcium content, while Yoda1 exacerbated these conditions.
• Yoda1 activation impaired HUVEC function, decreasing nitric oxide (NO) production and reducing eNOS, MMP-2, PCNA, and VEGFA expression.
• In co-cultures, Yoda1-activated HUVECs promoted calcification-related gene expression (SOX9, Runx2), increased alkaline phosphatase (ALP) activity, and enhanced calcium deposition in VSMCs.

Conclusions:

• Piezo1 channels in endothelial cells play a crucial role in the development of vascular calcification.
• Targeting Piezo1 presents a potential therapeutic strategy for preventing and treating vascular calcification.