Comparative effects of bevacizumab, ranibizumab and pegaptanib at intravitreal dose range on endothelial cells

Autor: Angela Carneiro, Raquel Soares, Paula Milheiro-Oliveira, Fernando Falcão-Reis, Ana Pirraco, Manuel Falcão
Přispěvatelé: Faculdade de Medicina, Faculdade de Engenharia
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Vascular Endothelial Growth Factor A
Medicina clínica [Ciências médicas e da saúde]
Angiogenesis
Pegaptanib
Drug Evaluation
Preclinical
Biotecnologia médica [Ciências médicas e da saúde]
Angiogenesis Inhibitors
Apoptosis
Pharmacology
Cell Movement
Phosphorylation
Cells
Cultured
Antibodies
Monoclonal
Aptamers
Nucleotide
Estatística
Engenharia biológica
Biotecnologia médica
Medicina clínica
Sensory Systems
Bevacizumab
Drug Combinations
Choroidal neovascularization
medicine.anatomical_structure
Clinical medicine [Medical and Health sciences]
Proteoglycans
Collagen
medicine.symptom
medicine.drug
Signal Transduction
Endothelium
Cell Survival
Neovascularization
Physiologic
Statistics
Biological engineering
Medical biotechnology
Clinical medicine
Antibodies
Monoclonal
Humanized
Cellular and Molecular Neuroscience
Ranibizumab
Medical biotechnology [Medical and Health sciences]
PEG ratio
medicine
Humans
Cell Proliferation
Dose-Response Relationship
Drug
business.industry
Vascular Endothelial Growth Factor Receptor-2
Capillaries
Ophthalmology
Immunology
Endothelium
Vascular
Laminin
business
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Popis: Anti-VEGF therapy proved to be useful against several ocular pathological situations, including choroidal neovascularization and proliferative retinopathies. Ranibizumab (Ran), Pegaptanib (Peg) and Bev-acizumab (Bev) are the pharmacological agents more frequently used in clinical practice by intravitreal injection. However, their exact effects on the angiogenic process have not been accurately established in a comparative study. The aim of the present study was to elucidate the precise effects of Ran, Peg and Bev on the multiple steps of the angiogenic process. Human umbilical vein endothelial cells (HUVEC) were incubated with each agent within the clinically established concentration range, or identical amounts of the excipients; cell cytotoxicity, proliferation, apoptosis, migration and vessel assembly were assessed. No cytotoxic effects were found for any of the agents studied at any concentration tested. At the clinical dose, cell proliferation was significantly reduced by Bev and Ran, whereas no difference was observed after Peg treatment. In addition, HUVEC apoptosis was effectively increased by Bev and Ran. Cell migration was reduced after incubation with every agent analyzed, though only reaching statistical significance upon Ran intravitreal dose. At clinical doses, capillary assembly was only affected by Bev. In agreement with these data, the active form of VEGF receptor-2 expression was decreased after incubation with Bev (to 66% of control values), Ran (78%) and Peg (86%) relative to controls. These findings indicate that these three agents display distinct effects on endothelial cells.
Databáze: OpenAIRE
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