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Type 2 cytokines promote angiogenesis in ischemic muscle via endothelial IL-4Rα signaling
- Source :
- Cell Reports, Vol 42, Iss 8, Pp 112964- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Summary: Peripheral arterial disease (PAD) is one of the leading causes of cardiovascular morbidity and mortality worldwide, yet current trials on therapeutic angiogenesis remain suboptimal. Type 2 immunity is critical for post-ischemic regeneration, but its regulatory role in revascularization is poorly characterized. Here, we show that type 2 cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), are the key mediators in post-ischemic angiogenesis. IL-4/IL-13-deficient mice exhibit impaired reperfusion and muscle repair in an experimental model of PAD. We find that deletion of IL-4Rα in the endothelial compartment, rather than the myeloid compartment, leads to remarkable impairment in revascularization. Mechanistically, IL-4/IL-13 promote endothelial cell proliferation, migration, and tube formation via IL-4Rα/STAT6 signaling. Furthermore, attenuated IL-4/IL-13 expression is associated with the angiogenesis deficit in the setting of diabetic PAD, while IL-4/IL-13 treatment rescues this defective regeneration. Our findings reveal the therapeutic potential of type 2 cytokines in treating patients with muscle ischemia.
- Subjects :
- CP: Metabolism
CP: Immunology
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 42
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8cc5c47f151048d685872f67046e9553
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2023.112964