title: Natriuretic peptide clearance receptor ligand (C-ANP4-23 ) attenuates angiogenesis in a murine sponge implant model.
abstract: Natriuretic peptide receptor-C activation by the synthetic ligand C-ANP-4-23, a specific agonist for this receptor, has been shown to inhibit key events of the angiogenic cascade, such as migration, proliferation and vascular endothelial growth factor (VEGF) production. In the present study we investigated whether C-ANP4-23 could also inhibit angiogenesis in the sponge model in vivo. To this end, we evaluated the effects of C-ANP4-23 on inflammatory and angiogenic components of the fibrovascular tissue induced by polyether polyurethane sponge implants in mice. Measurements of the haemoglobin content (μg/mg wet tissue) and blood flow (laser Doppler perfusion imaging) of the implants, used as an index of vascularization, revealed that single (200 ng) or multiple (200 ng/day, 5 days) doses of C-ANP4-23 reduced angiogenesis in the implants relative to the phosphate-buffered saline-treated group. The peptide exerted an inhibitory effect on nitric oxide production (nitrite levels) and had a dual effect on VEGF levels, depending on the number of doses (i.e. stimulation at 4 days after one dose; inhibition at 7 days after five doses). Histological analysis corroborated the biochemical and functional parameters indicative of inhibition of neovascularization (decreased vessel number) by C-ANP4-23 . The peptide failed to modulate inflammation in our system. The inhibitory effect of C-ANP4-23 on the angiogenic component of the fibrovascular tissue induced by the synthetic matrix extends the range of the its actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Almeida
authors.forename: Cibele C
authors.initials: CC
authors.lastname: Cardoso
authors.forename: Laura Aa
authors.initials: LA
authors.lastname: Orellano
authors.forename: Adelina M
authors.initials: AM
authors.lastname: Reis
authors.forename: Lucíola S
authors.initials: LS
authors.lastname: Barcelos
authors.forename: Silvia P
authors.initials: SP
authors.lastname: Andrade
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011140:Polyurethanes / Q000009:adverse effects; D012039:Regional Blood Flow; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D004343:Drug Implants; D006454:Hemoglobins; D018836:Inflammation Mediators; D010446:Peptide Fragments; D011140:Polyurethanes; D042461:Vascular Endothelial Growth Factor A; C115016:polyetherurethane; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor
keywords: angiogenesis; implants; inflammation; natriuretic peptides; nitric oxide; vascular endothelial growth factor