Relaxin-2 mitigates the interaction between monocytes and endothelial cells by suppressing Egr-1

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2025-04-07 DOI:10.1111/fcp.70007

Jing Bai, Hui Zhou

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引用次数: 0

Abstract

Background

An overproduction of oxidized low-density lipoprotein (ox-LDL) can lead to vascular endothelial dysfunction. Relaxin-2, a novel peptide hormone, exhibits various biological functions within the cardiovascular system. However, the effects of Relaxin-2 in atherosclerosis (AS) are underreported.

Objectives

We aimed to investigate the regulatory role of Relaxin-2 in the endothelial function of human aortic endothelial cells (HAECs) upon ox-LDL stimulation.

Methods

HAECs were stimulated with ox-LDL (100 mg/l) and rhRelaxin-2 (25, 50 nM) for 24 h. Multiple techniques, including real-time PCR, Western blot analysis, ELISA, and Calcein AM staining, were applied.

Results

Treatment with human recombinant (rh) Relaxin-2 decreased lectin-like ox-LDL receptor 1 (LOX-1), a primary receptor for ox-LDL, in HAECs. rhRelaxin-2 also reduced the ox-LDL-induced expression of pro-inflammatory mediators such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Additionally, we observed increased expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and high mobility group protein B1 (HMGB-1) in ox-LDL-challenged HAECs, which was diminished by rhRelaxin-2. Significantly, the heightened expression of intercellular cell adhesion molecule-1 (ICAM-1) and E-selectin in ox-LDL-stimulated HAECs was mitigated by rhRelaxin-2. Consequently, rhRelaxin-2 alleviated the attachment of THP-1 cells to HAECs in a dose-dependent manner. Mechanistically, we found that rhRelaxin-2 inhibited the expression of Egr-1, a central mediator of endothelial inflammation. Furthermore, overexpression of Egr-1 was found to negate the beneficial effects of rhRelaxin-2, suggesting that these effects are mediated by the suppression of Egr-1.

Conclusion

Our findings propose a novel therapeutic approach with rhRelaxin-2 for patients with atherosclerosis.

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松弛素-2通过抑制Egr-1减轻单核细胞和内皮细胞之间的相互作用

背景氧化低密度脂蛋白（ox-LDL）的过量产生可导致血管内皮功能障碍。松弛素-2是一种新型肽激素，在心血管系统中具有多种生物学功能。然而，松弛素-2在动脉粥样硬化（AS）中的作用被低估了。目的探讨松弛素-2在ox-LDL刺激下对人主动脉内皮细胞（HAECs）内皮功能的调节作用。方法用ox-LDL （100 mg/l）和rhRelaxin-2（25、50 nM）刺激HAECs 24h。使用多种技术，包括实时PCR， Western blot分析，ELISA和钙黄蛋白AM染色。结果人重组（rh）松弛素-2处理可降低haec中ox-LDL的主要受体凝集素样ox-LDL受体1 （LOX-1）。rhRelaxin-2还能降低ox- ldl诱导的促炎介质如白细胞介素6 （IL-6）、肿瘤坏死因子-α (TNF-α)和单核细胞趋化蛋白-1 （MCP-1）的表达。此外，我们观察到环氧化酶-2 （COX-2）、前列腺素E2 （PGE2）和高迁移率组蛋白B1 （HMGB-1）在ox- ldl挑战的haec中的表达增加，rhRelaxin-2降低了这种表达。值得注意的是，在ox- ldl刺激的haec中，细胞间细胞粘附分子-1 （ICAM-1）和e-选择素的表达升高被rhRelaxin-2缓解。因此，rhRelaxin-2以剂量依赖的方式减轻THP-1细胞对HAECs的附着。在机制上，我们发现rhRelaxin-2抑制Egr-1的表达，Egr-1是内皮炎症的中心介质。此外，研究发现Egr-1的过表达会抵消rhRelaxin-2的有益作用，这表明这些作用是通过抑制Egr-1介导的。结论本研究为动脉粥样硬化患者应用rhRelaxin-2提供了一种新的治疗方法。

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.