AMSCs-Derived MiR-222-Containing Exosomes Suppress Inflammation to Reduce Incidence of Aortic Dissection

Background: One of the pathogeneses of aortic dissection (AD) is inflammation-induced collagen deposition and elastin degradation. The transplantation of adipose-derived mesenchymal stem cells (AMSCs) can prevent AD via the action of paracrine mechanisms. This study aims to investigate how microRNA-222 (miR-222) and exosomes from AMSCs influence the evolution of fibrosis and inflammation in AD.Methods: AMSC-exosomes were isolated and identified. Subsequently, they were traced in vitro using the PKH67 staining method. In vivo testing was conducted using an AD model induced by & beta;-aminopropionitrile fumarate (BAPN) and angiotensin II (Ang II), and in vitro investigations were carried out utilizing aortic smooth muscle cells (SMCs). The miR-222 expression in AD patients, AD mice, and platelet-derived growth factor-BB (PDGF-BB)-treated SMCs after AMSC-exosome treatment was assessed by quantitative real-time PCR (qRT-PCR). A dual-luciferase reporter gene assay was used to determine the target relationship between miR-222 and G protein subunit alpha i3 (GNAI3). To better understand the role of inflammation and fibrosis throughout the course of AD, artificial activation and block experiments of miR-222 were carried out. The prevalence of AD, the survival rate, and histological stainings were utilized for evaluating the severity of AD between groups. Apart from proliferation, apoptosis and expression of inflammation factors were further evaluated using 5-Ethynyl-2'-Deoxyuridine (EdU), Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL), flow cytometry, qRT-PCR, and enzyme-linked Results: Exosomic-miR-222-mimic derived from AMSCs can be transferred into SMCs and decreased excessive proliferation and inflammation by targeting GNAI3-extracellular regulated protein kinases (ERK) signaling in vitro. Exosomic-miR-222 decreased a GNAI3 via direct binding to its 3 & PRIME;-untranslated region (3 & PRIME;-UTR). Meanwhile, in vivo testing showed that AMSC-derived exosomes can function in aortic tissues. Mice treated with exosomic-miR-222-mimic demonstrated a substantial decrease in the prevalence of AD and improved the level of fibrosis in the aorta, while its inhibition reversed this process.Conclusions: Exosomic-miR-222 functions as a regulator of AD progression and inflammation response by targeting the GNAI3ERK signaling pathway. Exosomic-miR-222 may, therefore, have therapeutic value in lowering sudden unfavorable AD episodes.

Automated summary

This study investigates the role of adipose-derived mesenchymal stem cell (AMSC) exosomes and microRNA-222 (miR-222) in the progression of aortic dissection (AD). The results show that exosomes from AMSCs can reduce excessive proliferation and inflammation in AD by targeting the GNAI3-ERK signaling pathway. In vivo testing demonstrates that exosomic-miR-222 can lower the prevalence of AD and improve fibrosis levels in the aorta. These findings suggest that exosomic-miR-222 may have therapeutic potential in reducing sudden adverse episodes of AD.