Oxidative Stress Related to Plasmalemmal and Mitochondrial Phosphate Transporters in Vascular Calcification

Nhung Thi Nguyen, Tuyet Thi Nguyen, Kyu Sang Park

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)


Inorganic phosphate (Pi) is essential for maintaining cellular function but excess of Pi leads to serious complications, including vascular calcification. Accumulating evidence suggests that oxidative stress contributes to the pathogenic progression of calcific changes. However, the molecular mechanism underlying Pi-induced reactive oxygen species (ROS) generation and its detrimental consequences remain unclear. Type III Na+-dependent Pi cotransporter, PiT-1/-2, play a significant role in Pi uptake of vascular smooth muscle cells. Pi influx via PiT-1/-2 increases the abundance of PiT-1/-2 and depolarization-activated Ca2+ entry due to its electrogenic properties, which may lead to Ca2+ and Pi overload and oxidative stress. At least four mitochondrial Pi transporters are suggested, among which the phosphate carrier (PiC) is known to be mainly involved in mitochondrial Pi uptake. Pi transport via PiC may induce hyperpolarization and superoxide generation, which may lead to mitochondrial dysfunction and endoplasmic reticulum stress, together with generation of cytosolic ROS. Increase in net influx of Ca2+ and Pi and their accumulation in the cytosol and mitochondrial matrix synergistically increases oxidative stress and osteogenic differentiation, which could be prevented by suppressing either Ca2+ or Pi overload. Therapeutic strategies targeting plasmalemmal and mitochondrial Pi transports can protect against Pi-induced oxidative stress and vascular calcification.

Original languageEnglish
Article number494
Issue number3
Publication statusPublished - 2022 Mar

Bibliographical note

Funding Information:
Funding: This work was supported by the Medical Research Center Program (2017R1A5A2015369) from the Ministry of Science, ICT, Korea.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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