MicroRNA-325 ameliorates angiotensin II-induced abdominal aortic aneurysm by inhibiting the endothelial-to-mesenchymal transition through regulation of the MAPK/SNAI1/MMP-2 pathway

Abstract

Objective

Angiotensin II (Ang II)-induced chronic inflammation can lead to the formation of abdominal aortic aneurysms (AAAs). Previous studies have revealed associations between endothelial-to-mesenchymal transition (EndMT) and microvascular diseases, but the association between EndMT and AAA formation remains unclear. In this study, the protective effects of miRNA-325 against Ang II-induced EndMT and AAA and the related mechanism were investigated.

Methods

A murine model of Ang II-induced AAA was used, and human aortic endothelial cells (HAECs) were used to study the underlying mechanism. Markers of EndMT and inflammation were studied both in vitro and in vivo. SNAI1 siRNA and miRNA-325 mimics were used to elucidate the role of EndMT in AAA formation and the possible protective effects of miRNA-325.

Results

In vitro, silencing of SNAI1 expression suppressed Ang II-induced EndMT. In vivo, Ang II-infused mice presented higher levels of SNAI1, α-SMA, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, and matrix metalloproteinase (MMP)-2 expression and lower levels of CD31 and VE-cadherin in the abdominal aorta than did control mice. Silencing SNAI1 expression decreased the incidence and severity of AAA and suppressed EndMT in Ang II-infused mice. Furthermore, the administration of miRNA-325 decreased the expression of SNAI1 and MMP-2 in Ang II-treated mice and ameliorated AAA.

Conclusions

Ang II contributes to EndMT and AAA in mice, and this effect can be prevented via the suppression of SNAI1 expression. MicroRNA-325 decreased the expression of SNAI1 and MMP-2 and ameliorated subsequent AAA by inhibiting EndMT.