| Abstrakt: |
Objective: To investigate the mechanism by which miR-301a accelerates the progression of angiotensin II (An-gII)-induced abdominal arterial aneurysm (AAA) by regulating macrophage M1 polarization through the PTEN/PI3K/AKT signaling pathway. Methods: In in vivo experiments, 8-10-week-old ApoE-/- male mice were divided into control, model, and miR-301a overexpression groups, and saline (saline) infusion was used as the control group (n=15), and the AAA model was built up by angiotensin II (Ang II) induction (77=45) ; THP-1 cells were randomly divided into the control group, Ang II + agomir NC group, Ang E +miR-301a agomir group and AngII+miR-301a agomir+LY (LY294002) group; the mechanism of miR-301a regulating macrophage polarization for aneurysm progression was elucidated by using bioinformatics, ELISA, Western blot, qRT-PCR, and dual lucifera.se reporter assay. Results: miR-301a expression was upregulated in the AAA group compared with the control, and all Ang II -injected mice exhibited larger aortic diameters. targetScan7.2 database predicted the existence of a binding site between miR-301a and PTEN, and dual-luciferase reporter gene analysis confirmed that miR-301a directly targeted the PTEN gene. GO and KEGG pathway analysis revealed that the pathway of PI3K/AKT/ and NF-κB signaling may be a key pathway for macrophage polarization toward Ml. In vivo and in vitro experiments demonstrated that miR-301a regulated macrophage polarization toward the Ml phenotype through inhibition of PTEN and activation of the PI3K/AKT signaling pathway upregulated the expression of matrix metalloproteinases and inflammatory factors, and promoted aneurysm progression. In addition, plasma miR-301a in combination with MMP-9's could be a candidate biomarker for predicting aneurysm rupture. Conclusions: miR-301a plays a key role in disease progression in AAA by promoting M1 polarization of macrophages via the PTEN/ PI3K/AKT pathway, thereby accelerating aneurysm progression. [ABSTRACT FROM AUTHOR] |
