The Calcimimetic R568 Reduces Vascular Smooth Muscle Cell Calcification in Vitro Via ERK 1/2 Phosphorylation

Background: Vascular calcification (VC) is a common complication of chronic kidney disease, ultimately leading to high morbidity and cardiovascular mortality. In this study, we investigated the effects of the calcimimetic R568 in an in vitro model of human vascular smooth muscle cell (VSMC) calcification. Methods: Human VSMCs were cultured under elevated calcium (2.4 mmol/L) and phosphate (2.7 mmol/L) concentrations. Calcification was analyzed using von Kossa staining and colorimetric calcium measurement. Intracellular signaling was examined via Western blot, and apoptosis was assessed by the TUNEL assay. Results: Treatment with R568 significantly reduced VC over the 9-day treatment period. R568 treatment led to increased phosphorylation of extracellular signal-regulated kinase (ERK 1/2) compared to the control group. Calcimimetic treatment was also associated with a reduction in apoptosis. Blocking ERK 1/2 phosphorylation completely abolished the inhibitory effects of R568 on VC. Conclusion: Our study provides new insights into the mechanism of action of calcimimetics during VC and highlights the importance of ERK 1/2 signaling in this process.