Impaired Autonomic Regulation of Resistance Arteries in Mice With Low Vascular Endothelial Growth Factor or Upon Vascular Endothelial Growth Factor Trap Delivery

Erik Storkebaum, Carmen Ruiz de Almodovar, Merlijn Meens, Serena Zacchigna, Massimiliano Mazzone, Greet Vanhoutte, Stefan Vinckier, Katarzyna Miskiewicz, Koen Poesen, Diether Lambrechts, Ger M. J. Janssen, Gregorio E. Fazzi, Patrik Verstreken, Jody Haigh, Paul M. Schiffers, Hermann Rohrer, Annemie Van Der Linden, Jo G. R. De Mey, Peter Carmeliet*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)

Abstract

Background-Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. Methods and Results-Here, we report that VEGF(partial derivative/partial derivative) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions. Conclusions-These findings uncover a novel role for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients. (Circulation. 2010; 122: 273-281.)
Original languageEnglish
Pages (from-to)273-U107
JournalCirculation
Volume122
Issue number3
DOIs
Publication statusPublished - 20 Jul 2010

Keywords

  • arteries
  • muscle, smooth
  • nervous system
  • vascular endothelial growth factor
  • vasoconstriction

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