Journal Article

The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification

Tang, Ke-Xin, Wu, Yun-Yun, Guo, Bei, Zhong, Jia-Yu, Duan, Jia-Yue, Shan, Su-Kang, Wang, Yi, Wu, Feng, Yuan, Ling-Qing, Xu, Feng, Ullah, Muhammad Hasnain Ehsan, Li, Fu-Xing-Zi, Liao, Xiao-Bo, Xu, Qiu-Shuang, Zheng, Ming-Hui, Ou-Yang, Wen-Lu, Lei, Li-Min, Lin, Xiao

2022

Overview

Arterial calcification is highly prevalent, particularly in patients with end-stage renal disease (ESRD). The osteogenic differentiation of vascular smooth muscle cells (VSMCs) is the critical process for the development of arterial calcification. However, the detailed mechanism of VSMCs calcification remains to be elucidated. Here, we investigated the role of exosomes (Exos) derived from endothelial cells (ECs) in arterial calcification and its potential mechanisms in ESRD. Accelerated VSMCs calcification was observed when VSMCs were exposed to ECs culture media stimulated by uremic serum or high concentration of inorganic phosphate (3.5 mM Pi). and the pro-calcification effect of the ECs culture media was attenuated by exosome depletion. Exosomes derived from high concentrations of inorganic phosphate-induced ECs (ECs HPi -Exos) could be uptaken by VSMCs and promoted VSMCs calcification. Microarray analysis showed that miR-670-3p was dramatically increased in ECs HPi -Exos compared with exosomes derived from normal concentrations of inorganic phosphate (0.9 mM Pi) induced ECs (ECs NPi -Exos). Mechanistically, insulin-like growth factor 1 (IGF-1) was identified as the downstream target of miR-670-3p in regulating VSMCs calcification. Notably, ECs-specific knock-in of miR-670-3p of the 5/6 nephrectomy with a high-phosphate diet (miR-670-3p EC-KI  + NTP) mice that upregulated the level of miR-670-3p in artery tissues and significantly increased artery calcification. Finally, we validated that the level of circulation of plasma exosomal miR-670-3p was much higher in patients with ESRD compared with healthy controls. Elevated levels of plasma exosomal miR-670-3p were associated with a decline in IGF-1 and more severe artery calcification in patients with ESRD. Collectively, these findings suggested that ECs-derived exosomal miR-670-3p could promote arterial calcification by targeting IGF-1, which may serve as a potential therapeutic target for arterial calcification in ESRD patients.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 13/1 / 13/89 / 13/95 / 14/34 / 14/5 / 59/5 / 631/80 / 64/60 / 692/699/75/593/2193 / Animals / Antibodies / Arteriosclerosis / Biochemistry / Biomedical and Life Sciences / Calcification / Calcification (ectopic) / Cell Biology / Cell Culture / Cell differentiation / Culture media / Culture Media - pharmacology / End-stage renal disease / Endothelial cells / Endothelial Cells - metabolism / Exosomes / Exosomes - metabolism / Immunology / Insulin / Insulin-like growth factor I / Insulin-Like Growth Factor I - metabolism / Insulin-like growth factors / Kidney diseases / Kidney Failure, Chronic - metabolism / Life Sciences / Mice / MicroRNAs - metabolism / Muscle, Smooth, Vascular - metabolism / Myocytes, Smooth Muscle - metabolism / Nephrectomy / Osteogenesis / Phosphates - metabolism / Phosphorus / Phosphorus - metabolism / Phosphorus - pharmacology / Smooth muscle / Therapeutic targets / Vascular Calcification - metabolism / Veins & arteries