Type 2 cytokines promote angiogenesis in ischemic muscle via endothelial IL-4Rα signaling

Autor: Huixian Li, Chufeng He, Ruiwen Zhu, Francis M. Chen, Lin Wang, Fung Ping Leung, Xiao Yu Tian, Gary Tse, Wing Tak Wong
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 8, Pp 112964- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112964
Popis: 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.
Databáze: Directory of Open Access Journals