Oxidative stress by Ca 2+ overload is critical for phosphate-induced vascular calcification

作者：Nhung Nguyen, Tuyet Thi Nguyen, Dat Da Ly, Jingbo Xia, Xu-Feng Qi, In‐Kyu Lee, Seung‐Kuy Cha, Kyu‐Sang Park · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2020 · DOI：10.1152/ajpheart.00305.2020 · 被引用次数：62 · 研究领域：Parathyroid Disorders and Treatments、Magnesium in Health and Disease、Ion Transport and Channel Regulation

The novel findings of this study are type III sodium-phosphate cotransporters PiT-1 and -2-dependent depolarization by high Pi, leading to Ca 2+ entry via voltage-gated Ca 2+ channels in vascular smooth muscle cells. Cytosolic Ca 2+ increase and subsequent oxidative stress are indispensable for osteogenic differentiation and calcification. In addition, plasmalemmal abundance of PiT-1/2 relies on Ca 2+ overload and oxidative stress, establishing a positive feedback loop. Identification of mechanistic components of a vicious cycle could provide novel therapeutic strategies against vascular calcification in hyperphosphatemic patients.