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Your search keyword '"Nawaz, Imtiaz M."' showing total 7 results
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7 results on '"Nawaz, Imtiaz M."'

6. <italic>N</italic>-<italic>tert</italic>-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors.

Author

Nawaz, Imtiaz M., Chiodelli, Paola, Rezzola, Sara, Paganini, Giuseppe, Corsini, Michela, Lodola, Alessio, Di Ianni, Alessio, Mor, Marco, and Presta, Marco

Subjects
FIBROBLAST growth factors, CARBONYL compound derivatives, NEOVASCULARIZATION, FORMYL peptide receptors, VASCULAR endothelial growth factors
Abstract

The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A). Our data demonstrate that BOC2, but not BOC1, inhibits the angiogenic activity of heparin-binding VEGF-A165 with no effect on the activity of the non-heparin-binding VEGF-A121 isoform. Endothelial cell-based bioassays, surface plasmon resonance analysis, and computer modeling indicate that BOC2 may interact with the heparin-binding domain of VEGF-A165, thus competing for heparin interaction and preventing the binding of VEGF-A165 to tyrosine kinase receptor VEGFR2, its phosphorylation and downstream signaling. In addition, BOC2 inhibits the interaction of a variety of heparin-binding angiogenic growth factors with heparin, including fibroblast growth factor 2 (FGF2) whose angiogenic activity is blocked by the compound. Accordingly, BOC2 suppresses the angiogenic potential of human tumor cell lines that co-express VEGF-A and FGF2. Thus, BOC2 appears to act as a novel multi-heparin-binding growth factor antagonist. These findings caution about the interpretation of FPR-focusing experimental data obtained with this compound and set the basis for the design of novel BOC2-derived, FPR independent multi-target angiogenesis inhibitors. [ABSTRACT FROM AUTHOR]

Published
2018
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7. Inflammation and N-formyl peptide receptors mediate the angiogenic activity of human vitreous humour in proliferative diabetic retinopathy

Author

Paola Chiodelli, Stefania Mitola, Daniela Coltrini, Sara Rezzola, Mirella Belleri, Mario De Rosa, Francesco Semeraro, Vincenzo Pavone, Anna Cancarini, Michela Corsini, Roberto Ronca, Marco Presta, Dario Rusciano, Imtiaz M. Nawaz, Luca Lista, Rezzola, Sara, Corsini, Michela, Chiodelli, Paola, Cancarini, Anna, Nawaz, Imtiaz M., Coltrini, Daniela, Mitola, Stefania, Ronca, Roberto, Belleri, Mirella, Lista, Liliana, Rusciano, Dario, de Rosa, Mario, Pavone, Vincenzo, Semeraro, Francesco, and Presta, Marco

Subjects
0301 basic medicine, Male, endocrine system diseases, Angiogenesis, Endocrinology, Diabetes and Metabolism, Endothelial cells, Pharmacology, Vitreous, Pathogenesis, Mice, Endocrinology, Endothelial cell, Diabetic retinopathy, Receptor, Aged, 80 and over, Neovascularization, Pathologic, Middle Aged, Diabetes and Metabolism, Angiogenesi, medicine.anatomical_structure, Inflammation, N-formyl peptide receptor, Internal Medicine, Female, medicine.symptom, Endothelium, Proinflammatory cytokine, Cell Line, 03 medical and health sciences, medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, cardiovascular diseases, Aged, Vitreou, Vitreous humour, business.industry, medicine.disease, Receptors, Formyl Peptide, eye diseases, Vitreous Body, 030104 developmental biology, Immunology, sense organs, business
Abstract

AIMS/HYPOTHESIS: Angiogenesis and inflammation characterise proliferative diabetic retinopathy (PDR), a major complication of diabetes mellitus. However, the impact of inflammation on the pathogenesis of PDR neovascularisation has not been elucidated. Here, we assessed the capacity of PDR vitreous fluid to induce pro-angiogenic/proinflammatory responses in endothelium and the contribution of the inflammation-related pattern recognition N-formyl peptide receptors (FPRs) in mediating these responses. METHODS: Pooled and individual pars plana vitrectomy-derived PDR vitreous fluid ('PDR vitreous') samples were assessed in endothelial cell proliferation, motility, sprouting and morphogenesis assays, and for the capacity to induce proinflammatory transcription factor activation, reactive oxygen species production, intercellular junction disruption and leucocyte-adhesion molecule upregulation in these cells. In vivo, the pro-angiogenic/proinflammatory activity of PDR vitreous was tested in murine Matrigel plug and chick embryo chorioallantoic membrane (CAM) assays. Finally, the FPR inhibitors Boc-Phe-Leu-Phe-Leu-Phe (Boc-FLFLF) and Ac-L-Arg-Aib-L-Arg-L-Cα(Me)Phe-NH2 tetrapeptide (UPARANT) were evaluated for their capacity to affect the biological responses elicited by PDR vitreous. RESULTS: PDR vitreous activates a pro-angiogenic/proinflammatory phenotype in endothelial cells. Accordingly, PDR vitreous triggers a potent angiogenic/inflammatory response in vivo. Notably, the different capacity of individual PDR vitreous samples to induce neovessel formation in the CAM correlates with their ability to recruit infiltrating CD45+ cells. Finally, the FPR inhibitor Boc-FLFLF and the novel FPR antagonist UPARANT inhibit neovessel formation and inflammatory responses triggered by PDR vitreous in the CAM assay. CONCLUSIONS/INTERPRETATION: This study provides evidence that inflammation mediates the angiogenic activity of PDR vitreous and paves the way for the development of FPR-targeting anti-inflammatory/anti-angiogenic approaches for PDR therapy.

Published
2017

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