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22-09-2023 | Arterial Occlusive Disease | CORRESPONDENCE

Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation

Authors: Wonjun Cho, Heeseung Oh, Sung Woo Choi, A. M. Abd El-Aty, Fatma Yeşilyurt, Ji Hoon Jeong, Tae Woo Jung

Published in: Inflammation | Issue 1/2024

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Abstract

Musclin, a myokine, undergoes modulation during exercise and has demonstrated anti-inflammatory effects in cardiomyocytes and glomeruli. However, its role in atherosclerotic responses remains unclear. This study aimed to explore the impact of musclin on inflammatory responses and the interaction between endothelial cells and monocytes under hyperlipidemic conditions. The attachment levels of THP-1 monocytes on cultured HUVECs were examined. Inflammation and the expression of cell adhesion molecules were also evaluated. To explore the molecular mechanisms of musclin, PPARα or heme oxygenase 1 (HO-1) siRNA transfection was performed in HUVECs. The results revealed that treatment with recombinant musclin effectively suppressed the attachment of palmitate-induced HUVECs to THP-1 cells and reduced the expression of cell adhesion proteins (ICAM-1, VCAM-1, and E-selectin) in HUVECs. Furthermore, musclin treatment ameliorated the expression of inflammation markers (phosphorylated NFκB and IκB) in both HUVECs and THP-1 monocytes, as well as the release of TNFα and MCP-1 from HUVECs and THP-1 monocytes. Notably, musclin treatment augmented the expression levels of PPARα and HO-1. However, when PPARα or HO-1 siRNA was employed, the beneficial effects of musclin on inflammation, cell attachment, and adhesion molecule expression were abolished. These findings indicate that musclin exerts anti-inflammatory effects via the PPARα/HO-1 pathway, thereby mitigating the interaction between endothelial cells and monocytes. This study provides evidence supporting the important role of musclin in ameliorating obesity-related arteriosclerosis and highlights its potential as a therapeutic agent for treating arteriosclerosis.

Graphical Abstract

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Metadata
Title
Musclin Mitigates the Attachment of HUVECs to THP-1 Monocytes in Hyperlipidemic Conditions through PPARα/HO-1-Mediated Attenuation of Inflammation
Authors
Wonjun Cho
Heeseung Oh
Sung Woo Choi
A. M. Abd El-Aty
Fatma Yeşilyurt
Ji Hoon Jeong
Tae Woo Jung
Publication date
22-09-2023
Publisher
Springer US
Published in
Inflammation / Issue 1/2024
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01904-4

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Keynote webinar | Spotlight on advances in lupus

  • Live
  • Webinar | 27-05-2025 | 18:00 (CEST)

Systemic lupus erythematosus is a severe autoimmune disease that can cause damage to almost every system of the body. Join this session to learn more about novel biomarkers for diagnosis and monitoring and familiarise yourself with current and emerging targeted therapies.

Join us live: Tuesday 27th May, 18:00-19:15 (CEST)

Prof. Edward Vital
Prof. Ronald F. van Vollenhoven
Developed by: Springer Medicine
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Webinar