Table 2.
Pro-angiogenic peptides.
| Pro-angiogenic peptide | Sequence | Source | Demonstrated effects | Reference |
|---|---|---|---|---|
| Qk | KLTWQELYQLKYKGI | α-helix region of VEGF | Causes similar signaling and in vitro effects to full-length VEGF. In vivo, Qk increased vessel density in ischemic hind limbs and Matrigel plugs, as well as the rate of cutaneous wound closure | Santulli et al. (2009), Finetti et al. (2012) |
| PAB2-1c | (C*VRKIEIVRKK)2–Ahx–Ahx–Ahx–RKRKLERIAR–NH2 | Mimic of PDGF | Stimulates cell proliferation, migration, and collagen gel contraction similar to full-length PDGF in vitro | Lin et al. (2007) |
| T7 vasculotide | (PEG-CHHHRHSF) tetramer | Tie-2-binding region of Ang1 | Increases serum-free cell survival and cell migration as compared to controls in vitro. Increases vessel number and size when delivered from Matrigel, and increase the rate of diabetic wound closure when delivered using Intrasite Topical Gel in vivo | Van Slyke et al. (2009), Slyke (2011) |
| GHK, GHK-Cu, or SPARC120-122 | GHK | Cu2+-binding region of SPARC | Induces a wide range of cellular effects, including reducing inflammatory while increasing anti-inflammatory factors, increasing extracellular matrix protein production, and matrix metalloproteinase expression. In vivo effects have been shown ranging from increasing vascularization in the rabbit eye, increasing the rate of uncomplicated and diabetic wound healing, and inhibiting gastric ulcer formation | Pickart (2008) |
| Comb1 | DINECEIGAPAGEETEVTVEGLEPG | Combination of the epidermal growth factor -like domains of fibrillin 1 and tenascin X | Increases cell proliferation, tube formation, and sprouting compared to controls in vitro. Increased chemically impaired cutaneous wound healing when co-delivered daily with UN3 | Demidova-Rice et al. (2011, 2012) |
| UN3 | NH2-ELLESYIDGRPTATSEYQTFFNPR-amide | Previously unknown peptide fragment from platelet lysate | Significantly increased cell migration, proliferation, and tube formation in vitro. Significantly increased vessel density in impaired cutaneous wounds. Increased chemically impaired cutaneous wound healing when co-delivered daily with Comb1 | Demidova-Rice et al. (2012) |
| KRX-725 | MRPYDANKR | Second intercellular loop of sphingosine 1-phosphate (S1P) 3 | Increases aortic ring sprouting as compared to controls with greater smooth muscle cell co-localization to endothelial cells than VEGF. Increases in vascularization of the rabbit cornea were obtained by co-treatment with KRX-725 and VEGF or bFGF as compared to factors alone | Ben-Sasson et al. (2003) |
| Pep-12 | NYLTHRQ | Ig-like domain II of VEGF receptor 1 | Facilitates integrin-mediated cell adhesion and cause tube formation in vitro. Significantly increases angiogenesis in the rabbit cornea as compared to controls, albeit to a lesser extent than VEGF | Soro et al. (2008) |
| LL-37 | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES | The 134–170 amino acid region of the human cationic anti-microbial protein 18 | Originally identified as an anti-microbial peptide produced in response to inflammation or infection, it was shown to have pro-angiogenic effects in addition to anti-microbial action. LL-37 caused dose-dependent increases in cell proliferation and increased collateral blood flow, capillary density, and blood velocity in a rabbit hind-limb ischemia model | Koczulla et al. (2003) |
| YR or RoY | YPHIDSLGHWRR | Identified by phage display for binding to endothelial cells | Increased cell proliferation and migration in vitro. Increases vessel density when injected into a mouse ear and hindlimb reperfusion when delivered intramuscularly | Hardy et al. (2007, 2008) |
| AcSDKP | AcSDKP | A naturally expressed regulator of hematopoiesis found in bone marrow | AcSDKP increases cell migration and tube formation, with increasing then decreasing responses as the concentration is increased beyond the optimal dose. Similar results were seen in vivo using the Matrigel plug assay, with greater vascularization induced with 10−9 M than 10−5 M of peptide | Liu et al. (2003) |
A selection of pro-angiogenic peptides, all which are in pre-clinical testing. Standard amino acid abbreviations are used. C*, disulfide bridge; Ahx, aminohexanoic acid; Ac, acetyl.