Exosomal NEDD4L derived from HG+oxLDL-induced vascular endothelial cells accelerates macrophage M1 polarization and oxLDL uptake by ubiquitinating IκBα and PPARγ

• DOI: 10.1007/s10565-024-09973-3
• Publication Date: 2025-01-07T05:58:35Z
• Authors: Guozhu Chen; Yisong Pei; Peng Jiang; Qiaoling Ye; Zulong Xie; Laxman Gyawali
• Keywords: Macrophage polarization; Exosome; Oil Red O; Foam cell

Vascular endothelial cell-derived exosomes are thought to mediate disease progression by regulating macrophage polarization. However, its mechanism in diabetes mellitus (DM)-related atherosclerosis (AS) progress is unclear. High-glucose (HG) and oxLDL were used induce human cardiac microvascular cells (HCMECs) mimic DM-related AS model. The conditioned medium (CM) from HG+oxLDL-induced HCMECs was incubated with THP1-M0 monocytes treated LPS or oxLDL. mRNA levels of M1/M2 polarization markers, NEDD4L, IκBα PPARγ determined qRT-PCR. Flow cytometry analyze marker. Dil-labeled oil red O staining performed assess uptake cells. inflammatory factors examined using ELISA. Transmission electron microscope for observing foam cell formation exosome morphology. protein p-Smad1/Smad1, p-Smad2/Smad2, p-IκBα/IκBα, p-P65/P65, anti-lipid metabolism-related NEDD4L tested western blot. interaction between assessed Co-IP assay. CM could promote M1 polarization, formation, inhibiter GW4869 eliminated these effects. overexpressed HCMECs, which be taken up Exosomal knockdown inhibited reducing the p-IκBα/IκBα p-P65/P65. reduce expression through ubiquitination. HCMECs-derived exosomal enhance ubiquitination facilitate uptake, thus accelerating AS.