In vivo properties of the proangiogenic peptide QK.
The main regulator of neovascularization is Vascular Endothelial Growth Factor (VEGF). We recently demonstrated that QK, a de novo engineered VEGF mimicking peptide, shares in vitro the same biological properties of VEGF, inducing capillary formation and organization. On these grounds, the aim of this study is to evaluate in vivo the effects of this small peptide. Therefore, on Wistar Kyoto rats, we evaluated vasomotor responses to VEGF and QK in common carotid rings. Also, we assessed the effects of QK in three different models of angiogenesis: ischemic hindlimb, wound healing and Matrigel plugs. QK and VEGF present similar endothelium-dependent vasodilatation. Moreover, the ability of QK to induce neovascularization was confirmed us by digital angiographies, dyed beads dilution and histological analysis in the ischemic hindlimb as well as by histology in wounds and Matrigel plugs. Our findings show the proangiogenic properties of QK, suggesting that also in vivo this peptide resembles the full VEGF protein. These data open to new fields of investigation on the mechanisms of activation of VEGF receptors, offering clinical implications for treatment of pathophysiological conditions such as chronic ischemia.
Santulli
Gaetano
G
Dipartimento di Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Cattedra di Medicina Interna, Università degli Studi Federico II di Napoli, Italy. gaetanosantulli@libero.it
Ciccarelli
Michele
M
Palumbo
Gianluigi
G
Campanile
Alfonso
A
Galasso
Gennaro
G
Ziaco
Barbara
B
Altobelli
Giovanna Giuseppina
GG
Cimini
Vincenzo
V
Piscione
Federico
F
D'Andrea
Luca Domenico
LD
Pedone
Carlo
C
Trimarco
Bruno
B
Iaccarino
Guido
G
D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D032701:Biomimetics; D002196:Capillaries / Q000187:drug effects; D017536:Carotid Artery, Common / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006614:Hindlimb / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D007511:Ischemia / Q000503:physiopathology; D007797:Laminin / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D015202:Protein Engineering; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
D001672:Biocompatible Materials; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D010455:Peptides; D011509:Proteoglycans; C544548:QK peptide, rat; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen