膦甲酸通过 Pit-1 减少高磷血症诱导的血管钙化。

Phosphonoformic acid reduces hyperphosphatemia-induced vascular calcification via Pit-1.

机构信息

Nephrology Department, Jingmen Central Hospital Affiliated to Hubei Minzu University, Jingmen, Hubei, China.

Nephrology Department, Jingmen Central Hospital Affiliated to Jingchu University of Technology, Jingmen, Hubei, China.

出版信息

J Int Med Res. 2024 Jan;52(1):3000605231222156. doi: 10.1177/03000605231222156.

DOI:10.1177/03000605231222156

PMID:38180904

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10771066/

Abstract

OBJECTIVE

This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC).

METHODS

Primary human aortic smooth muscle cells and rat aortic rings were cultured in Dulbecco's modified Eagle's medium supplemented with 0.9 mM or 2.5 mM phosphorus concentrations. Type III sodium-dependent phosphate cotransporter-1 (Pit-1) small interfering RNA and phosphonoformic acid (PFA), a Pit-1 inhibitor, were used to investigate the effects and mechanisms of Pit-1 on HPVC. Calcium content shown by Alizarin red staining, expression levels of Pit-1, and characteristic molecules for phenotypic transition of vascular smooth muscle cells were examined.

RESULTS

Hyperphosphatemia induced the upregulation of Pit-1 expression, facilitated phenotypic transition of vascular smooth muscle cells, and led to HPVC in cellular and organ models. Treatment with Pit-1 small interfering RNA or PFA significantly inhibited Pit-1 expression, suppressed phenotypic transition, and attenuated HPVC.

CONCLUSIONS

Our findings suggest that Pit-1 plays a pivotal role in the development of HPVC. The use of PFA as a Pit-1 inhibitor has the potential for therapeutic intervention in patients with HPVC. However, further rigorous clinical investigations are required to ensure the safety and efficacy of PFA before it can be considered for widespread implementation in clinical practice.

摘要

目的

本研究旨在探讨高磷血症诱导血管钙化（HPVC）的机制。

方法

在含有 0.9 mM 或 2.5 mM 磷浓度的 Dulbecco 改良 Eagle 培养基中培养原代人主动脉平滑肌细胞和大鼠主动脉环。使用 III 型钠依赖性磷酸盐协同转运蛋白-1（Pit-1）小干扰 RNA 和磷丙戊酸钠（PFA），一种 Pit-1 抑制剂，研究 Pit-1 对 HPVC 的作用和机制。通过茜素红染色检测钙含量、Pit-1 表达水平以及血管平滑肌细胞表型转化的特征分子。