(A) From Castermans et al32, under normoxic conditions with the presence of basic fibroblastic growth factor (b-FGF), IL-21 activates the STAT1 pathway, which results in angiostatic effects. (B) From our study, under HSS conditions, IL-21R is upregulated; IL-21 promotes STAT3 signaling, leading to increased BCL-2/BAX ratio, and results in increased endothelial cell survival and angiogenesis.