Vascular calcification (VC) causes cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) on maintenance dialysis treatment. Although many mechanisms have been proposed, their detailed effects remain incompletely understood. In this issue of the JCI, Li et al. examined the molecular mechanism of the protective role of SIRT6 in VC in patients with CKD. Using in vitro and animal models of CKD, the authors demonstrated that SIRT6 prevents VC by suppressing the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Mechanistically, SIRT6 bound and deacetylated the runt-related transcription factor 2 (Runx2), a key transcription factor for osteogenic differentiation, promoting its nuclear export for proteasome degradation. These studies provide a pathway in the pathogenesis of VC and justify investigating SIRT6 as a potential target in CKD.
Mohamed G. Atta