MicroRNA-98 inhibition accelerates the development of atherosclerosis via regulation of dysfunction of endothelial cell

ABSTRACT

Background

Atherosclerosis has been recognized as a chronic inflammation initiated by dysfunction of endothelial cell that contributes to the increased morbidity and mortality of severe cardiovascular events. The reported important role of microRNA-98 (miR-98) in regulation of endothelial cell behaviors prompt us to hypothesize that miR-98 could be involved in the process of atherosclerosis.

Methods and Results

The current research showed the miR-98 expression was gradually down-regulated in atherosclerotic mouse arteries isolated from ApoE ablation mice subjected to high fat diet. Additionally, a dramatically reduced miR-98 expression in endothelial cells administrated to oxidized low-density lipoprotein (Ox-LDL) but a slight down-regulated level was found in macrophages. Functionally, attenuated miR-98 expression promoted secretion of chemokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs) induced by Ox-LDL, which subsequently increased infiltration and pro-inflammatory genes expression of macrophages, as well as the foam cell formation. Mechanistically, in vitro experiments indicated that the endothelial cell dysfunction regulated by miR-98 knockdown was partially contributed by upregulated expression of HMGB1. Furthermore, the animal experiment with ApoE^−/− mice administrated with miR-98 inhibitor demonstrated that miR-98 silencing enhanced the atherosclerotic lesions in aorta and aortic sinus that were accompanied with increased adhesion molecules, chemokines, and pro-inflammatory markers expression.

Conclusion

MicroRNA-98 knockdown promoted endothelial cell dysfunction to affect the inflammatory state of macrophage and the development of atherosclerosis, at least partially, through direct targeting HMGB1. Collected, these data suggested that miR-98 could be a novel drug target for atherogenesis management.

KEYWORDS:

• MircroRNA-98
• Huvecs
• macrophages
• HMGB1
• atherosclerosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

Funding

This work was supported by grants from Relationship between oct stent restenosis and serum untargeted metabolomics substrate peaks (YYWS4791)