研究 PCS 通过 TLR4/TREM-1 损伤血管内皮细胞并促进动脉粥样硬化形成的机制。

Research on mechanism of PCS in damaging vascular endothelial cells and promoting formation of atherosclerosis via TLR4/TREM-1.

机构信息

Department of Cardiovascular Medicine, Taizhou People's Hospital, Taizhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7533-7542. doi: 10.26355/eurrev_201811_16295.

DOI:10.26355/eurrev_201811_16295

PMID:30468503

Abstract

OBJECTIVE

The study aimed to explore the effects of p-cresyl sulfate (PCS) of damaging vascular endothelial cells and promoting the formation of atherosclerosis in mice.

MATERIALS AND METHODS

The apolipoprotein E (ApoE)-/- mice were fed normally and with a high-fat diet; the ApoE-/- mice fed with high-fat diet were divided into two groups and treated with blank control and PCS, respectively. The aortic arch in each group was taken and underwent the oil red O staining, and the serum PCS content in each group was detected. The basic components of plaque were observed, including foam cells, lipid deposition, and cholesterol crystal. Moreover, human umbilical vein endothelial cells were cultured and divided into control group, PCS treatment group (PCS), PCS treatment with TLR4 overexpression group (PCS+TLR4+), and PCS treatment with TLR4 knock-out group (PCS+TLR4-). The degree of endothelial cell damage was detected using a cluster of differentiation CD42b-/CD31+ endothelial microparticles (EMPs), and expressions of Toll-like receptor 4 (TLR4), triggering receptor expressed on myeloid cells-1 (TREM-1), phosphorylated-endothelial nitric oxide synthase (p-eNOS), and tumor necrosis factor-α (TNF-α) in cells were detected via Polymerase Chain Reaction (PCR) and Western blotting.

RESULTS

The serum PCS concentration in high-fat ApoE-/- mice was increased, and the aortic arch sections of ApoE-/- mice treated with PCS displayed the evident atherosclerotic plaques. Experimental results of human umbilical vein endothelial cells showed that the activity of human umbilical vein endothelial cells treated with PCS declined, the expression levels of TLR4, TREM-1, and TNF-α were increased, while that of p-eNOS was decreased. After the TLR4 knockout, the above effects of PCS were reversed.

CONCLUSIONS

PCS damages vascular endothelial cells through TRL4/TREM-1, thereby accelerating the formation of atherosclerosis.

摘要

目的

本研究旨在探讨对甲酚硫酸酯（PCS）对血管内皮细胞的损伤作用及其促进动脉粥样硬化形成的影响。

材料和方法

载脂蛋白 E（ApoE）-/- 小鼠正常喂养和高脂喂养；高脂喂养的 ApoE-/- 小鼠分为两组，分别给予空白对照和 PCS 处理。取各组主动脉弓进行油红 O 染色，检测各组血清 PCS 含量。观察斑块的基本成分，包括泡沫细胞、脂质沉积和胆固醇结晶。此外，培养人脐静脉内皮细胞，分为对照组、PCS 处理组（PCS）、TLR4 过表达组（PCS+TLR4+）和 TLR4 敲除组（PCS+TLR4-）。用 CD42b-/CD31+内皮微颗粒（EMPs）检测内皮细胞损伤程度，通过聚合酶链反应（PCR）和 Western blot 检测细胞中 Toll 样受体 4（TLR4）、髓样细胞触发受体 1（TREM-1）、磷酸化内皮型一氧化氮合酶（p-eNOS）和肿瘤坏死因子-α（TNF-α）的表达。

结果

高脂 ApoE-/- 小鼠血清 PCS 浓度升高，PCS 处理的 ApoE-/- 小鼠主动脉弓切片显示明显的动脉粥样硬化斑块。人脐静脉内皮细胞实验结果表明，PCS 处理后人脐静脉内皮细胞活性下降，TLR4、TREM-1 和 TNF-α表达水平升高，p-eNOS 表达水平降低。TLR4 敲除后，PCS 的上述作用被逆转。