Dataset Information
MiR-4291 stabilized the vulnerable atherosclerotic plaques by degrading the MAPK1/ERK2 in ApoE-/- mice.
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ABSTRACT: Background
This study sought to explore the mechanism of action of the micro ribonucleic acid (miR)-4291 in stabilizing atherosclerotic (AS) plaques.Methods
An AS model of apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (HFD) was established. Oxidized low-density lipoprotein (ox-LDL) was used to induce an inflammatory response of RAW264.7 macrophages. The mice were divided into the normal diet (ND) + miR-4291 negative control (NC) group, the ND + miR-4291 mimic group, the HFD + miR-4291 NC group, and the HFD + miR-4291 mimic group. They were also classified into the miR-4291 NC group, the miR-4291 mimic group, the ox-LDL + miR-4291 NC group, and the ox-LDL + miR-4291 mimic group. The arterial plaque burden of the mice was assessed by hematoxylin-eosin staining and immunohistochemistry, and the expression of phosphorylated-extracellular signal-regulated kinase 2 (p-ERK2) and related proteins in the arterial plaques and RAW264.7 macrophages of the mice were detected by Western blotting.Results
Obvious plaques with massive macrophage infiltration were found in the aortic roots of the mice fed a HFD, and smooth muscle cells were found at the margin of the plaques. In the HFD + miR-4291 mimic group, the number of plaques and macrophages was significantly declined, but there were no significant changes in the smooth muscle cells compared to those in the HFD + miR-4291 NC group. The Western blot results showed that miR-4291 reduced the protein expression of p-ERK1-2, t-ERK1-2, TNF-α, MCP-1, MMP-1, MMP-3, and MMP-9 in the AS plaques and the ox-LDL-induced RAW264.7 macrophages of the mice fed a HFD.Conclusions
MiR-4291 reduced the expression of MMP-2/9 by inhibiting the activity of ERK2, which in turn increased the fibrous cap thickness and stabilized the vulnerable plaques in AS.
SUBMITTER: Jin Y
PROVIDER: S-EPMC9761127 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
MiR-4291 stabilized the vulnerable atherosclerotic plaques by degrading the MAPK1/ERK2 in ApoE<sup>-/-</sup> mice.
Annals of translational medicine 20221101 22
<h4>Background</h4>This study sought to explore the mechanism of action of the micro ribonucleic acid (miR)-4291 in stabilizing atherosclerotic (AS) plaques.<h4>Methods</h4>An AS model of apolipoprotein E-deficient (ApoE<sup>-/-</sup>) mice fed a high-fat diet (HFD) was established. Oxidized low-density lipoprotein (ox-LDL) was used to induce an inflammatory response of RAW264.7 macrophages. The mice were divided into the normal diet (ND) + miR-4291 negative control (NC) group, the ND + miR-4291 ...[more]