MiR-499a suppresses LPS-induced human vascular endothelial cell inflammatory response and apoptosis by regulating STAT1.

MicroRNAs (miRNAs) have been revealed to be involved in dysfunction and inflammatory conditions of vascular endothelial cells (ECs). However, the role of miR-499a in inflammatory responses and apoptosis of human umbilical vein endothelial cells (HUVECs) remains unclear. The expression of miR-499a and signal transducer and activator of transcription 1 (STAT1) was analyzed using quantitative real-time polymerase chain reaction or western blot assay, respectively. Cells apoptosis was determined by Flow cytometry. Western blot was used to evaluate the protein expression of STAT1, interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax) and Cleaved Caspase-3. The interaction between miR-499a and STAT1 was confirmed by bioinformatics analysis and luciferase reporter assay. The expression of miR-499a was significantly down-regulated, while the STAT1 level was obviously up-regulated in LPS-induced HUVECs. Overexpressed miR-499a inhibited LPS-activated expression of IL-6, VCAM-1 and ICAM-1, and protected HUVECs against LPS-induced apoptosis by suppressing the expression of Bax and cleaved caspase 3 expressions. However, STAT1 promoted LPS-induced inflammatory injury and apoptosis in HUVECs. In addition, STAT1 was predicted and confirmed to be a target of miR-499a, and rescue experiment indicated that STAT1 was involved in the miR-499a mediated protection on LPS-induced HUVECs inflammatory injury and apoptosis. MiR-499a protects HUVECs from LPS-induced inflammatory injury and apoptosis by regulating STAT1 expression, which providing a novel insight to assist researchers and clinicians in developing potential therapeutic strategies for sepsis.