The Ang-1 and Ang-2 genes are located on chromosome 8. Functional polymorphisms have not been identified in the Ang-1 gene, but three have been identified in the coding region of Ang-2 [72] . In ECs under stress, Ang-2 mRNA expression is induced by VEGF, fibroblast growth factor 2 and hypoxia [44, 73] . Upregulation of Ang-2 induced by VEGF and hypoxia can be abolished by inhibiting tyrosine kinase or mitogen-activated protein kinase [73] . Ang-2 mRNA expression can be downregulated by Ang-1, Ang-2, or transforming growth factor [74] . After inhibition of PI3K by wortmannin, Ang-2 mRNA production is induced by the transcription factor FOXO1 (forkhead box O1) [75] . EC-specific Ang-2 promoter activity is regulated by Ets-1 and the Ets family member Elf-1 [76, 77] . Because Tie2 signalling is required under circumstances that usually hamper cell metabolism, its promoter contains repeats that ensure transcription under difficult circumstances, including hypoxia [78] .