| First Author | Mantsounga CS | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 5 | Pages | 110309 |
| PubMed ID | 35108537 | Mgi Jnum | J:327097 |
| Mgi Id | MGI:6879562 | Doi | 10.1016/j.celrep.2022.110309 |
| Citation | Mantsounga CS, et al. (2022) Macrophage IL-1beta promotes arteriogenesis by autocrine STAT3- and NF-kappaB-mediated transcription of pro-angiogenic VEGF-A. Cell Rep 38(5):110309 |
| abstractText | 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-1beta. IL-1beta promotes pro-angiogenic VEGF-A165a isoform transcription via activation and promoter binding of STAT3 and NF-kappaB, as demonstrated by gene-deletion, gain-of-function, inhibition, and chromatin immunoprecipitation assays. Conversely, IL-1beta-deletion or inhibition of STAT3 or NF-kappaB increases anti-angiogenic VEGF-A165b isoform expression, indicating IL-1beta signaling may also direct splice variant selection. In an experimental PAD model of acute limb ischemia, macrophage IL-1beta expression is required for pro-angiogenic VEGF-A expression and for VEGF-A-induced blood flow recovery via angio- or arteriogenesis. Though further study is needed, macrophage IL-1beta-dependent transcription of VEGF-A via STAT3 and NF-kappaB may have potential to therapeutically promote angiogenesis in the setting of PAD. |
