Implications of Senescent Cell Burden and NRF2 Pathway in Uremic Calcification: A Translational Study.

ABSTRACT: Increased senescent cell burden and dysregulation of the nuclear factor erythroid 2-related factor 2 (NRF2) pathway have been associated with numerous age-related pathologies; however, their role in promoting vascular calcification (VC) in chronic kidney disease (CKD) has yet to be determined. We investigated whether senescence and NRF2 pathways may serve as drivers of uremia-induced VC using three complementary approaches: a novel model of induced VC in 5/6-nephrectomized rats supplemented with high phosphate and vitamin D; epigastric arteries from CKD patients with established medial calcification; and vascular smooth muscle cells (VSMCs) incubated with uremic serum. Expression of p16^Ink4a and p21^Cip1, as well as γ-H2A-positive cells, confirmed increased senescent c

SUBMITTER: Laget J 

PROVIDER: S-EPMC9954542 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature