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

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, PPARa 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 NF?B and I?B) in both HUVECs and THP-1 monocytes, as well as the release of TNFa and MCP-1 from HUVECs and THP-1 monocytes. Notably, musclin treatment augmented the expression levels of PPARa and HO-1. However, when PPARa 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 PPARa/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.

Dergi

INFLAMMATION

Yıl

2024

Cilt

47

Sayı

1

Sayfa

1-12

ISSN

0360-3997

eISSN

1573-2576

DOI

10.1007/s10753-023-01904-4

WoS UID

WOS:001071708900002