A second class of candidate genes represents monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor, which both act on monocytic cells to promote arteriogenesis. 8 Another option is the use of transcription factors, which are known to promote angiogenesis by targeting various proangiogenic genes such as, for example, hypoxia-inducible factor-1 or early growth response protein-1 (EGR-1). 9

Other proangiogenic factors activate integrin-dependent pathways to promote angiogenesis. These integrin-activatory proteins include the extracellular matrix protein Del-1, which coordinates integrin expression by homeobox genes. 10 Additionally, the family of CCN comprises potent proangiogenic factors such as Cyr61, which binds to av5, thereby promoting angiogenesis. 11 Since integrin-matrix interaction is crucial for controlled vessel development, the temporal regulation of proteins activating or inhibiting integrin signaling is essential for the process of adult neovascularization. Additionally, regulators of the wnt/frizzled pathway, as shown for the secreted frizzled-related protein FrzA, promote adult angiogenesis. 12 This effect was shown to be independent of VEGF.