Of the three main functions of the Ang/Tie system, it is mainly angiogenesis that has been evaluated as a therapeutic target. So far, the focus of Ang/Tie modulation has been on inhibiting angiogenesis related to malignant and ophthalmological diseases and to complications of diabetes [158, 159] . In peripheral arterial occlusive disease, stimulation of angiogenesis seems a logical strategy to attenuate the consequences of ongoing tissue ischaemia. In a rat model of hind limb ischaemia, combined delivery of Ang-1 and VEGF genes stimulated collateral vessel development to the greatest extent [160, 161] . Thus far, therapy directed at VEGF has reached the clinic, but not therapy directed at Ang/Tie [162] .