Myricetin inhibits vascular calcification in an in vitro model by modulating ferroptosis-related SLC7A11/GPX4 signaling.

Vascular calcification (VC) is a major complication of type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Myricetin, a natural flavonoid with reported cardiovascular protective properties, has not been fully evaluated in the context of diabetic VC. In this study, the effects of myricetin were examined in vascular smooth muscle cells (VSMCs) exposed to hyperglycemic and phosphate (Pi) conditions in vitro. Myricetin attenuated calcification in VSMCs under hyperglycemic/Pi conditions. It decreased the expression of osteogenic markers RUNX2 and BMP-2, while restoring the expression of contractile markers α-SMA and SM22-α. Myricetin also reduced inflammatory responses, as indicated by decreased interleukin-6 mRNA and NLRP3 protein expression. In addition, myricetin reduced oxidative stress by lowering intracellular reactive oxygen species and malondialdehyde levels, decreasing the Fe2+/Fe3+ ratio, and increasing the GSH/GSSG ratio. Furthermore, myricetin restored the expression of ferroptosis-related regulators, including SLC7A11, GPX4, and FTH1, which were reduced under hyperglycemic/Pi conditions. The protective effects of myricetin were partially reversed by ferroptosis inducers, suggesting the involvement of ferroptosis-related mechanisms. Collectively, these findings suggest that myricetin may inhibit vascular calcification in vitro and has therapeutic potential for diabetic vascular complications.