MiR-146a regulates inflammation and development in patients with abdominal aortic aneurysms by targeting CARD10.

Abstract

We present the expression of miR-146a in abdominal aortic aneurysms (AAA) patients, and its mechanism for regulating inflammation and development in AAA patients. The expression of miR-146a in serum, PBMC, and abdominal aorta tissues was measured in AAA patients. We found that level of miR-146a in the serum and its expression in AAA tissues were significantly higher than that in healthy people or normal abdominal aorta tissues. Pearson's method analysis showed that miRNA-146a in the serum of AAA patients was negatively correlated with serum TNF-α, IFN-γ and CRP, and was positively correlated with serum IL-10. The luciferase reporter gene system confirmed that miR-146a targeted inhibition of CARD10 expression in THP-1 and human umbilical vein endothelial cells (HUVECs), and miR-146a was negatively correlated with the expression of CARD10 in the tissues/PBMC of AAA patients. In PBMC of healthy people, over-expression of miR-146a by transferring miR-146a-mimic could increase the expression of SIRT1 but decreased the expression of p65 and the level of TNF-α secretion. Moreover, HUVECs cellular activity change by TNF-α in a dose-dependent manner. These results suggested that miR-146a suppressed the inflammation of peripheral blood in AAA patients by targeting CARD10, and miR-146a blocked the progression of AAA through CARD10/SIRT1/p65 pathway.