Lactate–CEBPB–CXCL12/p21 axis in AngII-treated vascular smooth muscle cells and human AAA tissue
In an AngII-induced VSMC injury model, lactate-linked histone lactylation raised CEBPB, which activated CXCL12 and p21, driving senescence, inflammation and macrophage polarization in vitro; human AAA tissue findings were correlative. [1]
Automatic summary · not editorially reviewed
The key findings
In AAA patient tissues and AngII-treated VSMCs, p21 and CXCL12 mRNA and protein levels were significantly upregulated. [1]
AngII increased senescence markers and SASP factors, which were reversed by 2-DG treatment or p21 knockdown. [1]
The authors describe the lactate-CEBPB-CXCL12/p21 axis as a candidate mechanism requiring validation in in vivo aneurysm models. [1]
The source at a glance
- Study type / format
- Abstract of a laboratory study with human tissue correlation
- Population / context
- Human AAA patient tissues and AngII-treated vascular smooth muscle cells in vitro
- Summary based on
- Study abstract
- Original publication
- October 4, 2026
AngII VSMC model and human AAA tissue comparison
The study used vascular smooth muscle cells (VSMCs) treated with angiotensin II (AngII) as an injury model. Lactate was measured by a colorimetric assay; oxygen consumption and extracellular acidification rates were also analyzed. In both AAA patient tissues and AngII-treated VSMCs, mRNA and protein levels of p21 and CXCL12 were significantly upregulated. The human tissue findings are described as correlative, not as proof of cause.
Supporting source [1]
Senescence, inflammation and macrophage polarization in vitro
Silencing p21 or CXCL12 attenuated AngII-induced VSMC apoptosis. AngII increased reactive oxygen species, SA-β-gal-positive cells, senescence-related P16 expression and SASP factors (IL-6, CCL2, MMP2, CCL7); these were reversed by 2-DG treatment or p21 knockdown. AngII also promoted pro-inflammatory cytokine secretion, alleviated by 2-DG or CXCL12 silencing. CXCL12 knockdown reduced AngII-induced M1 macrophage polarization and the inhibition of M2 polarization.
Supporting source [1]
H3K18 lactylation, CEBPB binding and candidate mechanism
H3K18 lactylation levels were elevated in AAA tissues and AngII-treated VSMCs. Lactate treatment increased CXCL12, p21 and CEBPB expression and H3K18 lactylation in VSMCs. H3K18la was enriched at the CEBPB promoter, upregulating it; CEBPB bound the CXCL12 and p21 promoters, enhancing their transcription, and lactate treatment further enhanced this binding. Overexpression of p21 or CXCL12 rescued the effects of CEBPB knockdown. The authors call the lactate-CEBPB-CXCL12/p21 axis a candidate mechanism whose role in AAA formation and progression requires validation in in vivo aneurysm models.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Most mechanistic experiments were in vitro in AngII-treated VSMCs; human AAA tissue findings are correlative, and the proposed axis has not been validated in in vivo aneurysm models.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Han Y, Wang J, Li R, Shi X, Zhou H, Wang M, Wu X, Yuan H. · europepmc.org · October 4, 2026