Development of a novel antimicrobial peptide, AG-30, with angiogenic properties.
The utility of various synthetic peptides has been investigated in clinical trials of the treatment of cancers, infectious diseases and endocrine diseases. In the process of functional gene screening with in silico analysis for molecules with angiogenic properties, we generated a small peptide, angiogenic peptide (AG)-30, that possesses both antimicrobial and pro-inflammatory activities. AG-30 has an alpha-helix structure with a number of hydrophobic or net positively charged amino acids and a propensity to fold into amphipathic structures. Indeed, AG-30 exhibited antimicrobial activity against various bacteria, induced vascular endothelial cell growth and tube formation in a dose-dependent manner and increased neovascularization in a Matrigel plug assay. As a result, AG-30 up-regulated expression of angiogenesis-related cytokines and growth factors for up to 72 hrs in human aortic endothelial cells. To further evaluate the angiogenic effect of AG-30 in vivo, we developed a slow-release AG-30 system utilizing biodegradable gelatin microspheres. In the ischaemic mouse hind limb, slow-release AG-30 treatment results in an increase in angiogenic score, an increase in blood flow (as demonstrated by laser Doppler imaging) and an increase in capillary density (as demonstrated by immunostaining with anti-CD31 antibody). These data suggest that the novel peptide, AG-30, may have therapeutic potential for ischaemic diseases.
Nishikawa
Tomoyuki
T
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Nakagami
Hironori
H
Maeda
Akito
A
Morishita
Ryuichi
R
Miyazaki
Nobuhiko
N
Ogawa
Toshihiro
T
Tabata
Yasuhiko
Y
Kikuchi
Yasushi
Y
Hayashi
Hiroki
H
Tatsu
Yoshiro
Y
Yumoto
Noboru
N
Tamai
Katsuto
K
Tomono
Kazunori
K
Kaneda
Yasufumi
Y
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000139:chemically induced / Q000628:therapy; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D011487:Protein Conformation; D011509:Proteoglycans / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D023181:Antimicrobial Cationic Peptides; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C542514:antimicrobial peptide AG-30; C059485:matrigel; D003094:Collagen