| Autor: |
Mantsounga, Chris S., Lee, Cadence, Neverson, Jade, Sharma, Sheila, Healy, Abigail, Berus, Joshua M., Parry, Crystal, Ceneri, Nicolle M., López-Giráldez, Francesc, Chun, Hyung J., Lu, Qing, Sellke, Frank, Choudhary, Gaurav, Morrison, Alan R. |
| Zdroj: |
Cell Reports; Feb2022, Vol. 38 Issue 5, pN.PAG-N.PAG, 1p |
| Abstrakt: |
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-A 165 a 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-A 165 b isoform expression, indicating IL-1β signaling may also direct splice variant selection. In an experimental PAD model of acute limb ischemia, macrophage IL-1β 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-1β-dependent transcription of VEGF-A via STAT3 and NF-κB may have potential to therapeutically promote angiogenesis in the setting of PAD. [Display omitted] • Macrophage VEGF-A expression depends on autocrine IL-1β expression and signaling • IL-1β signaling activates both STAT3 and NF-κB to promote VEGF-A transcription • STAT3 and NF-κB upregulate the pro-relative to the anti-angiogenic VEGF-A isoform • In a PAD model, macrophage IL-1β is required for VEGF-A-driven angio/arteriogenesis Mantsounga et al. show inflammatory macrophage IL-1β expression to be required for pro-angiogenic VEGF-A expression and consequent post-developmental angio- or arteriogenesis in an experimental model of peripheral artery disease. Autocrine IL-1β signaling promotes transcription of pro-angiogenic VEGF-A 165 a isoform expression relative to anti-angiogenic isoform, VEGF-A 165 b, through activation of STAT3 and NF-κB. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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