Increased Lipogenesis and Stearate Accelerate Vascular Calcification in Calcifying Vascular Cells

Abstract

Vascular calcification is recognized as an independent predictor of cardiovascular mortality, particularly in subjects with chronic kidney disease. However, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear. We have shown that activation of the farnesoid X receptor (FXR) blocks mineralization of bovine calcifying vascular cells (CVCs) and in ApoE knock-out mice with 5/6 nephrectomy. In contrast to FXR, this study showed that liver X receptor

Activating transcription factor 4 regulates stearate-induced vascular calcification

“…For phosphorylated (p-)ATF4 detection, the promoted mineralization of VSMCs compared with other fatty acids. Inhibition of acetyl-CoA carboxylase or acyl-CoA synthetase reduced mineralization of VSMCs, whereas inhibition of stearoyl-CoA desaturase (which converts stearate to oleate) promoted mineralization and osteoblastic differentiation ( 12 ). We also found that increased cholesterol synthesis and uptake by LXR and SREBP-1c activations contributed to vascular calcifi cation ( 13 ).…”

“…There are four reasons for using MOVAS-1 cells in this study, instead of the primary bovine calcifying vascular cells used in our previous studies ( 11,12 ). First, MOVAS-1 cells have been established as a cell culture model of vascular calcifi cation.…”

“…The regulation of mineralization by FXR and LXR agonists was highly correlated with changes in lipid accumulation, fatty acid synthesis, and the expression of sterol regulatory element binding protein-1 (SREBP-1). The rate of lipogenesis in VSMCs through the SREBP-1c-dependent pathway was reduced by FXR activation but increased by LXR activation ( 11,12 ). SREBP-1c overexpression promoted mineralization in VSMCs, whereas SREBP-1c DN inhibited alkaline phosphatase activity and mineralization induced by LXR agonists.…”

“…1A ) ( 12 ). Other fatty acids, such as palmitoleate, oleate, and vaccenate, did not affect mineralization of MOVAS-1 cells ( Fig.…”

“…Recent in vivo and in vitro studies have implicated the involvement of numerous positive and negative regulators, including serum phosphate, several lipid-derived molecules (saturated fatty acids, oxys-MOVAS-1 cells were treated with triacsin C (Enzo Life Sciences) and free fatty acid-BSA complexes. The fatty acid-BSA complexes were generated as previously described ( 12,26 ). The medium was changed every 2-3 days.…”