Angiogenic factors and inflammation in steroid-refractory acute graft-vs-host disease

Steroid-refractory acute graft-vs-host disease (aGVHD) remains a frequent and often fatal complication of allogeneic hematopoietic cell transplantation. Recent evidence suggests that angiogenic factors-growth factors that contribute to blood vessel development-may be involved in tissue healing and restitution after inflammatory insults such as aGVHD. However, some angiogenic factors may also be involved in inflammation and worsen clinical outcomes. In this review, we summarize the data relevant to angiogenic factors that may contribute to healing after aGVHD (epidermal growth factor and vascular endothelial growth factor A) and angiogenic factors that may promote inflammation after aGVHD (placental growth factor and follistatin). It is currently unknown whether changes in these factors are a cause or a consequence of aGVHD. Mechanistic studies in the coming years will clarify their roles and identify new pathways for improving outcomes in steroid-refractory aGVHD.