Hrigh Phosphorus Level Leads to Aortic Calcification via β-Catenin in Chronic Kidney Disease

Aims:Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. Methods: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mm, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/beta-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of beta-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectonnized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. Results: High Pi induced VSMC calcification, down-regulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/beta-catenin pathway and beta-catenin activity. beta-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that beta-catenin transcriptionally regulated Pitl, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that beta-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of beta-catenin in the rat model was investigated, we found that aortic calcification was reduced. Conclusion: These results suggest that beta-catenin is an important player in high phosphorus level-induced aortic calcification in CKD. (C) 2015 S. Karger AG, Basel