Conditioned Media of Choroid Plexus Epithelium Cells Attenuates High Pi-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated Signal Pathways.

Xin Hui,Lijun Zhang,Xianjun Wang,Tongtong Zhang,Zuncheng Zheng,Mei Wang,Shangyong Geng,Ji Liu,Mengen Wang,Weiwei Hu,Shijun Zhao

doi:10.3389/fphys.2021.607739

Abstract

Vascular calcification was an independent risk of cardiovascular and cerebrovascular diseases (CCDs). Studies reported that conditioned media of choroid plexus epithelium cells (CPECs-CM) showed potential neuroprotective effects. However, the protective effect of CPECs-CM against vascular calcification (VC) has not been reported yet. Herein, high phosphate (HPi)–induced calcification model in mouse aortic vascular smooth muscle cells (MOVAS) was established, and the protective effects and underlying mechanism of CPECs-CM against HPi-induced calcification were explored. The results indicated that CPEC cells were successfully isolated and cultured, and CPECs-CM co-treatment significantly inhibited HPi-induced calcification of MOVAS cells through blocking alkaline phosphatase activity and expression. CPECs-CM co-treatment also suppressed reactive oxide species–mediated DNA damage in HPi-treated MOVAS cells. Moreover, dysfunction of MAPKs and PI3K/AKT pathways both contributed to HPi-induced calcification of MOVAS cells, and CPECs-CM co-treatment attenuated HPi-induced calcification by normalizing MAPKs and PI3K/AKT expression. Taken together, our findings provide evidence that CPECs-CM had the potential to inhibit vascular calcification with potent application in chemoprevention and chemotherapy of human CCD.

Highlights

Vascular calcification was accepted as a common pathological feature of atherosclerosis, diabetes, hypertension, kidney disease, and aging
Choroid plexus was observed by H&E staining, and the result indicated that choroid plexus showed a bunch-of-grapes appearance (Figure 1A1)
Previous studies have confirmed that CPECs-CM showed prominent neuroprotective effects, and infusion of CPECs had the potential to suppress ischemic damage to the brain (Borlongan et al, 2004; Matsumoto et al, 2010)

Summary

Introduction

Vascular calcification was accepted as a common pathological feature of atherosclerosis, diabetes, hypertension, kidney disease, and aging. Vascular calcification usually occurs in the vascular wall, and was associated with aging, diabetes, and kidney disease (Disthabanchong and Srisuwarn, 2019; Proudfoot, 2019). Increased evidence suggested that the generation of apoptotic corpuscles by apoptosis of vascular smooth muscle cells can act as nucleating structures and initiate vascular calcification (Wang et al, 2018). Oxidative stress activates endoplasmic reticulum stress in vascular smooth muscle cells, leading to increased apoptosis and vascular calcification (Ducy et al, 1997; Liu et al, 2014). The exogenous hydrogen peroxide can induce calcification in vascular smooth muscle cells via regulating Runx and PI3K/AKT signaling (Mody et al, 2001; Byon et al, 2008). Activation of p38 MAPK could induce bone cell differentiation and bone formation through interacting with Runx in response to oxidative stress (Yang et al, 2018)

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