The Effect of Alpha-Ketoglutarate on High Phosphate-Induced Calcification of Vascular Smooth Muscle Cells

Abstract

This thesis investigated whether alpha-ketoglutarate (α-KG) can prevent vascular calcification, a harmful process in which calcium deposits accumulate in blood vessel walls, especially in chronic kidney disease and diabetes. The study used human vascular smooth muscle cells and mouse aortic tissue exposed to high phosphate levels, which normally trigger calcification. Results showed that α-KG significantly reduced calcium deposition, with higher concentrations almost completely preventing calcification in cultured cells. α-KG also decreased the expression of osteogenic markers (Runx2 and Sox9) while restoring the contractile marker SM22α, indicating that it prevented smooth muscle cells from transforming into bone-like cells. In mouse aortic rings, α-KG reduced phosphate-induced calcification by about 40%, confirming its protective effect in intact vascular tissue. Overall, the findings suggest that α-KG is a promising metabolic compound that may help prevent vascular calcification, although further studies are needed to clarify its exact mechanisms and therapeutic potential.