Endothelial Cell-Dependent Regulation of Arteriogenesis
Rationale: Arteriogenesis is the process of formation of arterial conduits. Its promotion is an attractive therapeutic strategy in occlusive atherosclerotic diseases. Despite the and clinical importance of arteriogenesis, the biology of the process is poorly understood. Synectin, a gene previously implicated in the regulation of VEGF signalling, offers a unique opportunity to determine relative contributions of various cell types to arteriogenesis.
Objective: We investigated the cell autonomous effects of a synectin knockout in arterial morphogenesis.
Methods and Results: A "floxed" synectin knock-in mouse line was cross-bred with endothelial (Tie2, Cdh5, Pdg fb) and smooth muscle (Sm-MHC)- specific Cre driver mouse lines to produce cell type specific deletions. Ablation of synectin expression in endothelial but not smooth muscle cells resulted in the presence of developmental arterial morphogenetic defects (smaller size of the arterial tree, reduced number of arterial branches and collaterals) and impaired arteriogenesis in adult mice.
Conclusions: Synectin modulates developmental and adult arteriogenesis in an endothelial cell-autonomous fashion. These findings show for the first time that endothelial cells are central to both developmental and adult arteriogenesis and provide a model for future studies of factors involved in this process.
- endothelial cells
- vascular endothelial growth factor
- vascular endothelial growth factor receptor
- Received March 9, 2013.
- Revision received July 25, 2013.
- Accepted July 29, 2013.