Targeting the PI3K/Akt/NF-κB axis: Cluster of differentiation 5-like-mediated immunometabolic regulation of macrophage polarization in abdominal aortic aneurysm.

ABSTRACT: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder lacking effective pharmacological interventions. We identified CD5 molecule-like (CD5L) as a regulator of macrophage polarization in AAA via the phosphoinositide 3-kinase/protein kinase B/nuclear factor kappa B (PI3K/Akt/NF-κB) pathway. Transcriptomic analyses (GSE47472 and GSE57691) and angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE^-/-) mice showed CD5L upregulation, inversely correlated with M1 macrophage infiltration. In vitro CD5L overexpression reduced, whereas knockdown increased M1 polarization and pro-inflammatory cytokines in RAW264.7 cells and human monocyte-derived macrophages. In vivo, CD5L knockdown aggravated aortic dilation, vascular disruption, and inflammatory mediator expre

SUBMITTER: Yi H 

PROVIDER: S-EPMC12484710 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature