Abstract 8510: Regulation of Microrna-155 of the Atherosclerotic Inflammatory Responses by Targeting Map3k10
Objectives and Aims: There are increasing evidence that many miRNAs play important roles in cell proliferation, apoptosis and differentiation which accompany immno-inflammatory responses, and as all know that immuno-inflammation is thought to be a major contributor to atherogenesis.This study aims to investigate the potential role of microRNA on the atherosclerosis (AS) immuno-inflammatory mechanism.
Methods and results: The miRNA transcriptome was verified by TaqMan Real-time PCR assay with thoracic aorta sample from western-type diet fed APOE knockdown mice and plasma sample from coronary artery disease(CAD)patients.miR-155, miR-146a, miR-9 were aberrantly upregulated in APOE knockdown mice and miR-155, miR-146a, miR-29a were dysregulted in patients with CAD. In particular, miR-155 level was the most significantly elevated both in AS mice and in CAD patients relative to normol control. Moreover, we showed that miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production , lipid uptake and decreases atherosclerosis progression in the oxLDL-treated human monocytic cell line THP-1 and atherosclerotic model mice.(figure) Bioinformatics analysis suggested that mitogen-activated protein kinase kinase kinase 10(MAP3K10) maybe a potential target of miR-155, this was also confirmed by a luciferase reporter assay. Significantly, we suggested an additional explanation for the mechanism of miR-155 mediate immuno-inflammatory response and MAPK pathway by targeting mitogen-activated protein kinase kinase kinase 10.
Conclusions: miR-155 contributes to prevent AS development and progression and may be involved in the posttranscriptional regulation of the immno-inflammatory response and MAPK pathway by targeting MAP3K10
- © 2011 by American Heart Association, Inc.