3 FTI-277 inhibits vascular calcification by activating downstream Pi3k/Akt signalling and preventing apoptosis of vascular smooth muscle cells

Vascular calcification, which involves the osteogenic differentiation of vascular smooth muscle cells (VSMC), is a major contributor to morbidity and mortality in patients with atherosclerosis, diabetes and end-stage kidney disease. We have shown that nitrogen-containing bisphosphonates attenuate vascular calcification by inhibiting farnesylpyrophosphate synthase, thereby depleting cells of farnesylpyrophosphate and geranylgeranylpyrophosphate which are essential for the prenylation and activation of small GTPases. This study aims to determine whether vascular calcification is regulated by protein prenylation. We demonstrate that a farnesyl transferase inhibitor, FTI-277, significantly inhibits β-glycerophosphate-induced calcification of VSMC in a dose-dependent manner (p