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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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.