Lipopolysaccharide amplifies the endocytosis of circulating exosomes derived from aortic dissection patients by the endothelial cells via a JMJD6 dependent manner.

AIM: The underlying mechanism of endothelial dysfunction during the aortic dissection (AD) remains unclear. The present study is aimed to uncover the intrinsic mechanism regulating the endocytosis of circulating exosomes by endothelial cells after AD takes place.

MATERIAL AND

METHODS

Circulating exosomes extracted from both AD-patients and healthy donors (HD) were characterized and applied to human umbilical vein endothelial cells (HUVECs) in vitro with or without the co-exposure of lipopolysaccharide (LPS). The endocytosis of exosomes and inflammatory severity were evaluated. Besides, the JMJD6 expression pattern was explored, and si-RNA to knock down the JMJD6 expression was performed to test its role in exosome endocytosis.

KEY FINDINGS: Here, it was firstly shown that circulating exosomes of the AD patients were statistically higher than the HD. In vitro, the endocytosis of both AD- and HD-exosomes was both enhanced under the co-existence of the LPS, and the uptake of AD-exosomes instead of the control exosomes further worsened the LPS-induced cell injury and gene transcriptions of serial pro-inflammatory cytokines through the p65 signaling. Notably, LPS challenged ECs exhibited increased JMJD6 expression, and silencing JMJD6 effectively decreased the LPS enhanced exosome endocytosis, and attenuated the LPS + AD-exosomes induced cell pro-inflammatory injury.

SIGNIFICANCE: The findings above indicate that LPS co-exposure enhances the AD-exosomes endocytosis by the ECs and further aggravates the inflammatory injury; Targeting on the cellular JMJD6 shall mitigate AD-exosomes endocytosis, which might serve as a potential therapeutic approach for the endothelial dysfunction.