Histone lactylation-induced GLI3 activation drives macrophage M1 polarization and exosomal SERPINE1 release in abdominal aortic aneurysm progression.

ABSTRACT: M1 macrophages promote the progression of abdominal aortic aneurysm (AAA). Lactate-mediated histone lactylation modification regulates macrophage M1 polarization. However, the role and molecular mechanisms of lactylation-mediated macrophage M1 polarization in AAA remain unclear. Histone lactylation in macrophages was investigated using clinical specimens and AAA animal models, with subsequent validation at the cellular level. Key genes undergoing lactylation modification were screened through RNA-seq and CUT&Tag joint analysis. Functional validation was conducted to demonstrate that the target genes mediate AAA progression by regulating macrophage M1 polarization and subsequent exosome-mediated endothelial dysfunction. We observed elevated serum lactate levels in AAA patients. H3K18 lactyl

SUBMITTER: Yuan K 

PROVIDER: S-EPMC12603228 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature