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 differential/ partial differential) 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.
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 differential/ partial differential) 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 cancerpatients.
Authors: Carmen Ruiz de Almodovar; Pierre J Fabre; Ellen Knevels; Cathy Coulon; Inmaculada Segura; Patrick C G Haddick; Liesbeth Aerts; Nicolas Delattin; Geraldine Strasser; Won-Jong Oh; Christian Lange; Stefan Vinckier; Jody Haigh; Coralie Fouquet; Chengua Gu; Kari Alitalo; Valerie Castellani; Marc Tessier-Lavigne; Alain Chedotal; Frederic Charron; Peter Carmeliet Journal: Neuron Date: 2011-06-09 Impact factor: 17.173
Authors: Isabelle Brunet; Emma Gordon; Jinah Han; Brunella Cristofaro; Dong Broqueres-You; Chun Liu; Karine Bouvrée; Jiasheng Zhang; Raquel del Toro; Thomas Mathivet; Bruno Larrivée; Julia Jagu; Laurence Pibouin-Fragner; Luc Pardanaud; Maria J C Machado; Timothy E Kennedy; Zhen Zhuang; Michael Simons; Bernard I Levy; Marc Tessier-Lavigne; Almut Grenz; Holger Eltzschig; Anne Eichmann Journal: J Clin Invest Date: 2014-06-17 Impact factor: 14.808
Authors: Christian Lange; Erik Storkebaum; Carmen Ruiz de Almodóvar; Mieke Dewerchin; Peter Carmeliet Journal: Nat Rev Neurol Date: 2016-07-01 Impact factor: 42.937