In vivo properties of the proangiogenic peptide QK

Santulli, Gaetano; Ciccarelli, Michele; Palumbo, Gianluigi; Campanile, Alfonso; Galasso, Gennaro; Ziaco, Barbara; Altobelli, Giovanna Giuseppina; Cimini, Vincenzo; Piscione, Federico; D’Andrea, Luca Domenico; Pedone, Carlo; Trimarco, Bruno; Iaccarino, Guido

doi:10.1186/1479-5876-7-41

Cited by 105 publications

(110 citation statements)

References 35 publications

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“…The designed 15-mer peptide assumes in water a well defined helical conformation and presents a remarkable thermal stability (30,31). It binds and activates VEGF receptors and shows VEGF-like activity in vitro (29) and in vivo (32,33). Here, we extended this approach to the ␤5-␤6 hairpin region.…”

Section: Discussionmentioning

confidence: 99%

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

Diana

Basile

Rosa

et al. 2011

Journal of Biological Chemistry

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VEGF receptors have been the target of intense research aimed to develop molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure of the complex placental growth factor-VEGF receptor 1 D2 , we designed a VEGF receptor-binding peptide reproducing the placental growth factor ␤-hairpin region Gln 87 -Val 100 that is involved in receptor recognition. A conformational analysis showed that the designed peptide adopts the expected fold in pure water. Moreover, a combination of NMR interaction analysis and cell binding studies were used to demonstrate that the peptide targets VEGF receptors. The VEGF receptor 1 D2 -interacting residues were characterized at the molecular level, and they correspond to the residues recognizing the placental growth factor sequence Gln -Val 100. Finally, the peptide biological activity was characterized in vitro and in vivo, and it showed a VEGF-like behavior. Indeed, the peptide activated VEGF-dependent intracellular pathways, induced endothelial cell proliferation and rescue from apoptosis, and promoted angiogenesis in vivo. This compound is one of the few peptides known with proangiogenic activity, which makes it a candidate for the development of a novel peptide-based drug for medical applications in therapeutic angiogenesis.

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Section: Discussionmentioning

confidence: 99%

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

Diana

Basile

Rosa

et al. 2011

Journal of Biological Chemistry

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“…The chest was shaved with a depilatory cream (Veet, Reckitt-Benckiser). 15 Left ventricular (LV) end-diastolic and LV end-systolic diameters (LVEDD and LVESD, respectively) were measured at the level of the papillary muscles from the parasternal short-axis view as recommended. 16 Intraventricular septal (IVS) and LV posterior wall thickness (PW) were measured at end diastole.…”

Section: Echocardiographymentioning

confidence: 99%

Intracardiac Injection of AdGRK5-NT Reduces Left Ventricular Hypertrophy by Inhibiting NF-κB–Dependent Hypertrophic Gene Expression

et al. 2010

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Abstract-Several studies underline the role of the transcription factor NF-B in the development of left cardiac hypertrophy (LVH). We have demonstrated recently that the RGS homology domain within the amino terminus of GRK5 (GRK5-NT) is able to inhibit NF-B transcription activity and its associated phenotypes. The aim of this study was to evaluate the ability of GRK5-NT to regulate LVH through the inhibition of NF-B both in vitro and in vivo. In cardiomyoblasts, GRK5-NT inhibits phenylephrine-induced transcription of both NF-B and atrial natriuretic factor promoters, assessed by luciferase assay, thus confirming a role for this protein in the regulation of cardiomyocyte hypertrophy. In vivo, we explored 2 rat models of LVH, the spontaneously hypertensive rat and the normotensive Wistar Kyoto rat exposed to chronic administration of phenylephrine. Intracardiac injection of an adenovirus encoding for GRK5-NT reduces cardiac mass in spontaneously hypertensive rats and prevents the development of phenylephrineinduced LVH in Wistar Kyoto rats. This associates with inhibition of NF-B signaling (assessed by NF-B levels), transcriptional activity and phenotypes (fibrosis and apoptosis). Such phenomenon is independent from hemodynamic changes, because adenovirus encoding for GRK5-NT did not reduce blood pressure levels in spontaneously hypertensive rats or in Wistar Kyoto rats. In conclusion, our study supports the regulation of LVH based on the GRK5-NT inhibition of the NF-B transduction signaling. (Hypertension. 2010;56:696-704.)Key Words: cardiac hypertrophy Ⅲ intracardiac injection Ⅲ spontaneously hypertensive rats Ⅲ NF-B Ⅲ transcription factors N F-B is an ubiquitously expressed transcription factor that modulates the expression of genes involved in the regulation of cell functions, such as survival, apoptosis, growth, division, innate immunity, differentiation, and cellular responses to stress, hypoxia, and ischemia. 1-4 The classic cellular model in which this factor is studied is the immune system for its central role in cytokine production. 4,5 It has been reported recently that NF-B is relevant in the development of left ventricular hypertrophy (LVH) and remodeling through mechanisms independent from inflammation. NF-B mediates hypertrophic growth of cardiomyocytes in response to G protein-coupled receptor agonists, including norepinephrine, endothelin 1, and angiotensin II. 6,7 Also, NF-B inhibition attenuates LVH in different animal models of disease. 8,9 This evidence suggests that NF-B blockade may be an effective strategy to inhibit LVH and remodeling. The family of G protein-coupled receptor kinases (GRKs) and, in particular GRK2 and GRK5, possesses the ability to bind both NF-B and its inhibitor, IB␣. 10,11 In particular, GRK5, by means of its RGS homology (RH) domain within the amino terminus, interacts with IB␣ leading to the stabilization and accumulation of the IB␣/NF-B complex in the nucleus and, consequently, to the inhibition of NF-B transcriptional activity. 11 This feature of the RH domain of GR...

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“…56, 75 Other peptides have been designed as mimics of growth factors (e.g., angiopoietin, 76,77 VEGF, 78 and TGFb1 79 ) or as novel delivery systems.…”

Section: -70mentioning

confidence: 99%

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

Xiao

Ahadian

Radišić

2017

Tissue Engineering Part B: Reviews

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Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

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In vivo properties of the proangiogenic peptide QK

Cited by 105 publications

References 35 publications

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

Intracardiac Injection of AdGRK5-NT Reduces Left Ventricular Hypertrophy by Inhibiting NF-κB–Dependent Hypertrophic Gene Expression

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

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