ADA and sickle cell disease: Adenosine and the A2B receptor amplify HIF signaling under hypoxic conditions, contributing to further stabilisation of HIF protein and activation of HIF-mediated transcription in neuroendocrine enterochromaffin cells of the gut [50], smooth muscle cells [32], oral squamous cell carcinoma cells [51], cardiomyocytes [33] and microglial cells [52], as well as in adenosine deaminase-deficient mice and in vivo models of sickle cell disease [32].