Chenglei Zhang1, Haohua Wang1, Bin Yang2. 1. Department of Vascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China. 2. Department of Vascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China - yangbing20120210@sina.com.
Abstract
BACKGROUND: We present the expression of miR-146a in abdominal aortic aneurysms (AAA) patients, and its mechanism for regulating inflammation and development in AAA patients. METHODS: The expression of miR-146a in serum, PBMC, and abdominal aorta tissues was measured in AAA patients. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: We present the expression of miR-146a in abdominal aortic aneurysms (AAA) patients, and its mechanism for regulating inflammation and development in AAA patients. METHODS: The expression of miR-146a in serum, PBMC, and abdominal aorta tissues was measured in AAA patients. RESULTS: 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. CONCLUSIONS: 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.
Authors: Emma Plana; Laura Gálvez; Pilar Medina; Silvia Navarro; Victoria Fornés-Ferrer; Joaquín Panadero; Manuel Miralles Journal: Int J Mol Sci Date: 2020-06-28 Impact factor: 5.923