Hypoxia is induced by the metabolic demand of the increasing number of leukocytes recruited into the RA joints, which can lead to the accumulation of HIF-1α in the cytoplasm, and induces the expression and secretion of VEGF by macrophages as well as RA synovial tissue fibroblasts [8, 44]. The gene discussed is VEGFA; the disease is rheumatoid arthritis.