Functional and pharmacological characterization of a VEGF mimetic peptide on reparative angiogenesis

Finetti, Federica; Basile, Anna; Capasso, Domenica; Gaetano, Sonia Di; Stasi, Rossella Di; Pascale, Maria; Turco, Maria Caterina; Ziche, Marina; Morbidelli, Lucia; D’Andrea, Luca Domenico

doi:10.1016/j.bcp.2012.04.011

Cited by 90 publications

(88 citation statements)

References 39 publications

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“…28 In soluble form, the QK peptide has been reported to demonstrate angiogenic bioactivity above a threshold concentration of about 1 pM. 6,28,29 The QK peptide has also demonstrated bioactivity across a broad range of concentrations (1 pM-100 mM) when presented as a substrate-bound peptide on collagen scaffolds via collagenbinding peptides, 30 on hydroxyapatite via binding of an osteocalcin sequence, 29 and on self-assembled monolayers via covalent immobilization. 31 Keeping the MITCH network polymers unmodified, affinity immobilization is achieved simply by synthesizing a fusion of QK to a single proline-rich domain (P1), which acts as an affinity tag (Fig.…”

Section: Introductionmentioning

confidence: 97%

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

Mulyasasmita

Cai

Hori

et al. 2014

Tissue Engineering Part A

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Peptide mimics of growth factors represent an emerging class of therapeutic drugs due to high biological specificity and relative ease of synthesis. However, maintaining efficacious therapeutic dosage at the therapy site has proven challenging owing to poor intestinal permeability and short circulating half-lives in the blood stream. In this work, we present the affinity immobilization and controlled release of QK, a vascular endothelial growth factor (VEGF) mimetic peptide, from an injectable mixing-induced two-component hydrogel (MITCH). The MITCH system is crosslinked by reversible interactions between WW domains and complementary proline-rich peptide modules. Fusion of the QK peptide to either one or two units of the proline-rich sequence creates bifunctional peptide conjugates capable of specific binding to MITCH while preserving their angiogenic bioactivity. Presenting two repeats of the proline-rich sequence increases the binding enthalpy 2.5 times due to avidity effects. Mixing of the drug conjugates with MITCH components results in drug encapsulation and extended release at rates consistent with the affinity immobilization strength. Human umbilical vein endothelial cells (HUVECs) treated with the soluble drug conjugates exhibit morphogenetic events of VEGF receptor 2 signal transduction followed by cell migration and organization into networks characteristic of early angiogenesis. In a three-dimensional model where HUVECs were cultured as spheroids in a matrix of collagen and fibronectin, injection of drug-releasing MITCH resulted in significantly more cell outgrowth than drugs injected in saline. This ability to sustain local drug availability is ideal for therapeutic angiogenesis applications, where spatiotemporal control over drug distribution is a key requirement for clinical success.

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Section: Introductionmentioning

confidence: 97%

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

Mulyasasmita

Cai

Hori

et al. 2014

Tissue Engineering Part A

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“…Only a small number of VEGF residues are important for binding to VEGF receptors [18,25], and, therefore, several molecules able to modulate VEGF biological activities have been reported [26]. Many VEGF mimetic peptides with antiangiogenic activity have been described [27], while very few molecules with pro-angiogenic activity have been reported [28].…”

Section: Introductionmentioning

confidence: 99%

The Inorganic Perspective of VEGF: Interactions of Cu2+ with Peptides Encompassing a Recognition Domain of the VEGF Receptor

Grasso

Santoro

Magrı̀

et al. 2016

Journal of Inorganic Biochemistry

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“…Therefore, the primary aim of this study was to investigate the therapeutic effectiveness of liposomal angiogenic peptides in the treatment of cerebral ischemia. To achieve this goal, the present study used angiogenic peptides instead of proteins to treat cerebral ischemia because, unlike angiogenic proteins, peptides have low production costs with no immunogenicity and are better suited for clinical use (5,6). 18 F-FDG, a glucose analog with a hydroxyl group in position 29 replaced by a positron-emitting radioactive isotope 18 F, is commonly used as a marker for tissue glucose uptake; as such, it provides a sensitive and reliable means of assessing glucose metabolism.…”

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confidence: 99%

Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of ¹⁸F-FDG PET Imaging in Ischemic Stroke Treatment

Hwang¹,

Jeong²,

Na³

et al. 2015

J Nucl Med

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Strategies to promote angiogenesis can benefit cerebral ischemia. We determined whether liposomal delivery of angiogenic peptides with a known biologic activity of vascular endothelial growth factor benefitted cerebral ischemia. Also, the study examined the potential of 18 F-FDG PET imaging in ischemic stroke treatment. Methods: Male Sprague-Dawley rats (n 5 40) underwent 40 min of middle cerebral artery occlusion. After 15 min of reperfusion, the rats (n 5 10) received angiogenic peptides incorporated into liposomes. Animals receiving phosphate-buffered solution or liposomes without peptides served as controls. One week later, 18 F-FDG PET imaging was performed to examine regional changes in glucose utilization in response to the angiogenic therapy. The following day, 99m Tchexamethylpropyleneamine oxime autoradiography was performed to determine changes in cerebral perfusion after angiogenic therapy. Corresponding changes in angiogenic markers, including von Willebrand factor and angiopoietin-1 and -2, were determined by immunostaining and polymerase chain reaction analysis, respectively. Results: A 40-min period of middle cerebral artery occlusion decreased blood perfusion in the ipsilateral ischemic cortex of the brain, compared with that in the contralateral cortex, as measured by 99m Tchexamethylpropyleneamine oxime autoradiography. Liposomal delivery of angiogenic peptides to the ischemic hemisphere of the brain attenuated the cerebral perfusion defect compared with controls. Similarly, vascular density evidenced by von Willebrand factorpositive staining was increased in response to angiogenic therapy, compared with that of controls. This increase was accompanied by an early increase in angiopoietin-2 expression, a gene participating in angiogenesis. 18 F-FDG PET imaging measured at 7 d after treatment revealed that liposomal delivery of angiogenic peptides facilitated glucose utilization in the ipsilateral ischemic cortex of the brain, compared with that in the controls. Furthermore, the change in regional glucose utilization was correlated with the extent of improvement in cerebral perfusion (r 5 0.742, P 5 0.035). Conclusion: Liposomal delivery of angiogenic peptides benefits cerebral ischemia. 18 F-FDG PET imaging holds promise as an indicator of the effectiveness of angiogenic therapy in cerebral ischemia.

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Functional and pharmacological characterization of a VEGF mimetic peptide on reparative angiogenesis

Cited by 90 publications

References 39 publications

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

The Inorganic Perspective of VEGF: Interactions of Cu2+ with Peptides Encompassing a Recognition Domain of the VEGF Receptor

Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of ¹⁸F-FDG PET Imaging in Ischemic Stroke Treatment

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Functional and pharmacological characterization of a VEGF mimetic peptide on reparative angiogenesis

Cited by 90 publications

References 39 publications

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

Avidity-Controlled Delivery of Angiogenic Peptides from Injectable Molecular-Recognition Hydrogels

The Inorganic Perspective of VEGF: Interactions of Cu2+ with Peptides Encompassing a Recognition Domain of the VEGF Receptor

Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of 18F-FDG PET Imaging in Ischemic Stroke Treatment

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Improving Cerebral Blood Flow Through Liposomal Delivery of Angiogenic Peptides: Potential of ¹⁸F-FDG PET Imaging in Ischemic Stroke Treatment