MiR-339-3p promotes AT1-AA-induced vascular inflammation by upregulating NFATc3 protein expression in vascular smooth muscle cells.

Abstract

Vascular inflammation induced by angiotensin II-1 receptor autoantibody (AT1-AA) is involved in the occurrence and development of various cardiovascular diseases. miR-339-3p is closely related to the degree of vasodilation of aortic aneurysm and is also involved in the occurrence and development of acute pancreatitis. However, it is still unclear whether miR-339-3p influences AT1-AA-induced vascular inflammation. In this study, the role and mechanism of miR-339-3p in AT1-AA-induced vascular inflammation are studied. RT-PCR detection shows that the miR-339-3p levels in the thoracic aorta and serum exosomes of AT1-AA-positive rats are significantly increased. The miRwalk database predicts the mRNAs that miR-339-3p can bind to their 5'UTR. Subsequently, it is found that the number of genes contained in the T cell receptor pathway is high through KEGG analysis, and NFATc3 among them can promote the secretion of various inflammatory cytokines. AT1-AA-induced upregulation of miR-339-3p expression in vascular smooth muscle cells (VSMCs) can lead to a significant increase in NFATc3 protein level and promote vascular inflammation. Inhibition of miR-339-3p with antagomir-339-3p can significantly reverse AT1-AA-induced high expressions of IL-6, IL-1β and TNF-α proteins in rat thoracic aorta and VSMCs. That is, AT1-AA can upregulate the expression of miR-339-3p in VSMCs, and the increased miR-339-3p targets the 5'UTR of NFATc3 mRNA to increase the protein level of NFATc3, thereby aggravating the occurrence of vascular inflammation. These findings provide new experimental evidence for the involvement of miRNAs in regulating vascular inflammatory diseases.