Inhibition of mitochondrial phosphate carrier prevents high phosphate-induced superoxide generation and vascular calcification.

ABSTRACT: Vascular calcification is a serious complication of hyperphosphatemia that causes cardiovascular morbidity and mortality. Previous studies have reported that plasmalemmal phosphate (Pi) transporters, such as PiT-1/2, mediate depolarization, Ca²⁺ influx, oxidative stress, and calcific changes in vascular smooth muscle cells (VSMCs). However, the pathogenic mechanism of mitochondrial Pi uptake in vascular calcification associated with hyperphosphatemia has not been elucidated. We demonstrated that the phosphate carrier (PiC) is the dominant mitochondrial Pi transporter responsible for high Pi-induced superoxide generation, osteogenic gene upregulation, and calcific changes in primary VSMCs isolated from rat aortas. Notably, acute incubation with high Pi markedly increased the prot

SUBMITTER: Thi Nguyen N 

PROVIDER: S-EPMC10073177 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature