Bezafibrate mitigates oxidized-low density lipoprotein (ox-LDL)-induced the attachment of monocytes to endothelial cells: An implication in atherosclerosis

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2024-07-15 DOI:10.1111/fcp.13025

Huijun Huang, Yan Shen

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引用次数: 0

Abstract

Background

Oxidized forms of low-density lipoproteins (ox-LDL)-associated endothelial dysfunction and subsequent monocyte adhesion play an important role in the development of atherosclerosis (AS). Bezafibrate (BEZ) is a peroxisome proliferator-activated receptor (pan-PPAR) agonist licensed as a hypolipidemic drug. However, the effects of BEZ on endothelial dysfunction are less reported.

Objectives

In this study, we aim to investigate the protective effects of BEZ on ox-LDL-challenged vascular endothelial cells to evaluate its potential value in treating AS.

Methods

Human aortic endothelial cells (HAECs) and THP-1 cells were used to establish an In Vitro AS model. Cell Counting Kit-8 (CCK-8) assay, Real-time PCR, Western blot analysis, and Enzyme-linked immunosorbent assay (ELISA) were used to test the data.

Results

As expected, treatment with BEZ suppressed the expression of vascular endothelial growth factor A (VEGF-A), tissue factor (TF), Interleukin 12 (IL-12), tumor necrosis factor (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). BEZ was also found to inhibit ox-LDL-induced expression of the endothelial adhesion molecules vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HAECs. Correspondingly, BEZ prevented attachment of THP-1 monocytes to ox-LDL-incubated HAECs. Mechanically, BEZ was found to prevent NF-κB activation by reducing the levels of nuclear NF-κB p65 and inhibiting luciferase activity of NF-κB.

Conclusion

Our study revealed the pharmacological function of BEZ in protecting endothelial dysfunction against ox-LDL, which may provide valuable insight for the clinical application of BEZ.

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贝扎贝特可减轻氧化低密度脂蛋白（ox-LDL）诱导的单核细胞对内皮细胞的附着：对动脉粥样硬化的影响。

背景：与氧化形式的低密度脂蛋白（ox-LDL）相关的内皮功能障碍和随后的单核细胞粘附在动脉粥样硬化（AS）的发展中起着重要作用。贝扎贝特（Bezafibrate，BEZ）是一种过氧化物酶体增殖体激活受体（pan-PPAR）激动剂，已被许可作为降血脂药物。然而，有关 BEZ 对内皮功能障碍的影响的报道较少：方法：使用人主动脉内皮细胞（HAECs）和 THP-1 细胞建立体外 AS 模型。方法：用人主动脉内皮细胞（HAECs）和THP-1细胞建立体外强直性脊柱炎模型，采用细胞计数试剂盒-8（CCK-8）检测、实时PCR、Western印迹分析和酶联免疫吸附试验（ELISA）检测数据：正如预期的那样，BEZ能抑制血管内皮生长因子A（VEGF-A）、组织因子（TF）、白细胞介素12（IL-12）、肿瘤坏死因子（TNF-α）和单核细胞趋化蛋白-1（MCP-1）的表达。研究还发现，BEZ 能抑制氧化-LDL 诱导的 HAECs 内皮粘附分子血管细胞粘附分子-1（VCAM-1）和细胞间粘附分子-1（ICAM-1）的表达。相应地，BEZ 能阻止 THP-1 单核细胞附着在氧化-LDL 诱导的 HAECs 上。通过降低核 NF-κB p65 的水平和抑制 NF-κB 的荧光素酶活性，BEZ 被发现能从机制上阻止 NF-κB 的活化：我们的研究揭示了 BEZ 保护内皮功能障碍免受 ox-LDL 影响的药理作用，这可能会为 BEZ 的临床应用提供有价值的启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.