Exosomal miR-27b-3p secreted by visceral adipocytes contributes to endothelial inflammation and atherogenesis

Autor: Yan Tang, Li-Jie Yang, Hao Liu, Yan-Jue Song, Qi-Qi Yang, Yang Liu, Shu-Wen Qian, Qi-Qun Tang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 1, Pp 111948- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.111948
Popis: Summary: Obesity, particularly increased visceral fat, positively correlates with various metabolic challenges, including atherosclerosis, but the mechanism is not fully understood. The aim of this study is to determine the role of visceral-fat-derived exosomes (Exo) in endothelial cells and atherosclerosis. We show that obesity changes the miRNA profile of visceral adipose exosomes in mice. Importantly, exosomal miR-27b-3p efficiently enters into the vascular endothelial cells and activates the NF-κB pathway by downregulating PPARα. Mechanistically, miR-27b-3p binds directly to the CDS region of PPARα mRNA, thereby promoting mRNA degradation and suppressing translation. In ApoE-deficient mice, administration of miR-27b-3p mimic increases inflammation and atherogenesis, while overexpression of PPARα protects against atherosclerosis. Thus, obesity-induced exosomal miR-27b-3p promotes endothelial inflammation and facilitates atherogenesis by PPARα suppression. We reveal an exosomal pathway by which obesity aggravates atherosclerosis and proposed therapeutic strategies for atherosclerosis in people with obesity.
Databáze: Directory of Open Access Journals