{"title":"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。","authors":"Huijun Huang, Yan Shen","doi":"10.1111/fcp.13025","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bezafibrate mitigates oxidized-low density lipoprotein (ox-LDL)-induced the attachment of monocytes to endothelial cells: An implication in atherosclerosis\",\"authors\":\"Huijun Huang, Yan Shen\",\"doi\":\"10.1111/fcp.13025\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Human aortic endothelial cells (HAECs) and THP-1 cells were used to establish an In Vitro AS model. 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引用次数: 0
摘要
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。
Bezafibrate mitigates oxidized-low density lipoprotein (ox-LDL)-induced the attachment of monocytes to endothelial cells: An implication in atherosclerosis
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.
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
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Gene Therapy
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Lipids, Atherosclerosis
Liver and G-I Tract Pharmacology
Metabolism, Pharmacokinetics
Neuropharmacology
Neuropsychopharmacology
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Pediatric Pharmacology Development
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Pharmacoepidemiology
Pharmacogenetics, Pharmacogenomics
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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.
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