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dc.contributor.authorNguyen, Thi Nhung
dc.contributor.authorNguyen, Thi Tuyet
dc.contributor.authorNguyen, Thu Ha
dc.contributor.authorLee, Ji-Min
dc.contributor.authorKim, Min-Ji
dc.contributor.authorQi, Xu-Feng
dc.contributor.authorCha, Seung-Kuy
dc.contributor.authorLee, In-Kyu
dc.contributor.authorPark, Kyu-Sang
dc.date.accessioned2024-12-23T13:48:18Z
dc.date.available2024-12-23T13:48:18Z
dc.date.issued2023-03-01
dc.identifier.urihttps://vinspace.edu.vn/handle/VIN/475
dc.description.abstractVascular 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 protein abundance of PiC via ERK1/2- and mTOR-dependent translational upregulation. Genetic suppression of PiC prevented Pi-induced ERK1/2 activation, superoxide production, osteogenic differentiation, and vascular calcification of VSMCs in vitro and aortic rings ex vivo. Pharmacological inhibition of mitochondrial Pi transport using butyl malonate (BMA) or mersalyl abolished all pathologic changes involved in high Pi-induced vascular calcification. BMA or mersalyl also effectively prevented osteogenic gene upregulation and calcification of aortas from 5/6 subtotal nephrectomized mice fed a high-Pi diet. Our results suggest that mitochondrial Pi uptake via PiC is a critical molecular mechanism mediating mitochondrial superoxide generation and pathogenic calcific changes, which could be a novel therapeutic target for treating vascular calcification associated with hyperphosphatemia.en_US
dc.language.isoen_USen_US
dc.titleInhibition of mitochondrial phosphate carrier prevents high phosphate-induced superoxide generation and vascular calcificationen_US
dc.typeArticleen_US


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  • Nguyen Thi Tuyet, MD., PhD. [4]
    Assistant Professor, Program Director, Internal Medicine Residency Program, College of Health Sciences

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