Macrophage IL-1β promotes arteriogenesis by autocrine STAT3- and NF-κB-mediated transcription of pro-angiogenic VEGF-A.

ABSTRACT: Peripheral artery disease (PAD) leads to considerable morbidity, yet strategies for therapeutic angiogenesis fall short of being impactful. Inflammatory macrophage subsets play an important role in orchestrating post-developmental angiogenesis, but the underlying mechanisms are unclear. Here, we find that macrophage VEGF-A expression is dependent upon the potent inflammatory cytokine, IL-1β. IL-1β promotes pro-angiogenic VEGF-A₁₆₅a isoform transcription via activation and promoter binding of STAT3 and NF-κB, as demonstrated by gene-deletion, gain-of-function, inhibition, and chromatin immunoprecipitation assays. Conversely, IL-1β-deletion or inhibition of STAT3 or NF-κB increases anti-angiogenic VEGF-A₁₆₅b isoform expression, indicating IL-1β signaling may also direct

SUBMITTER: Mantsounga CS 

PROVIDER: S-EPMC8865931 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature