VEGFASubscript165/Subscript Potently Induces

Authors: Chetan Lakshmana Reddy Nejla Yosef Eroboghene E Ubogu

Publish Date: 2013/05/26

Volume: 33, Issue: 6, Pages: 789-801

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Abstract

Several mitogens such as vascular endothelial growth factor VEGF have been implicated in mammalian vascular proliferation and repair However the molecular mediators of human bloodnerve barrier BNB development and specialization are unknown Primary human endoneurial endothelial cells pHEndECs were expanded in vitro and specific mitogen receptors detected by western blot pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin Nonradioactive cell proliferation Matrigel™induced angiogenesis and sterile micropipette injury wound healing assays were performed Proliferation rates number and total length of induced microvessels and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions VEGFA165 in the presence of heparin was the most potent inducer of pHEndEC proliferation angiogenesis and wound healing in vitro 131 nM VEGFA165 induced ~110  increase in cell proliferation relative to basal conditions ∼51  without heparin 262 pM VEGFA165 induced a threefold increase in mean number of microvessels and 39fold increase in total capillary length/field relative to basal conditions In addition 026 nM VEGFA165 induced ∼13fold increased average rate of endothelial wound healing 4–18 h after endothelial monolayer injury mediated by increased cell migration VEGFA165 was the only mitogen capable of complete wound closure occurring within 30 h following injury via increased cell proliferation This study demonstrates that VEGFA165 in the presence of heparin is a potent inducer of pHEndEC proliferation angiogenesis and wound healing in vitro VEGFA165 may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injurySpecial thanks to Dr Monique Stins for providing THBMECs Aspects of this study were presented in part in abstract form at the 2011 American Academy of Neurology meeting Honolulu Hawaii USA and the 2011 Peripheral Nerve Society meeting Potomac Maryland USA This study was supported by a Baylor College of Medicine New Investigator StartUp Award 2007–2011 The Neuromuscular Immunopathology Research Laboratory is currently supported by the National Institutes of Health Grants R21 NS073702 R21 NS078226 and R01 NS075212 and a subaward P30 AI27767 to EEU The funding sources had no involvement in the conduct of the research manuscript preparation data collection/analyses or decision to submit this work for publication The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

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