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Circ Res. 2013 Oct 12;113(9):1076-86. doi: 10.1161/CIRCRESAHA.113.301340. Epub 2013 Jul 29.

Endothelial cell-dependent regulation of arteriogenesis.

Author information

1
From the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, New Haven, CT.

Abstract

RATIONALE:

Arteriogenesis is the process of formation of arterial conduits. Its promotion is an attractive therapeutic strategy in occlusive atherosclerotic diseases. Despite the functional and clinical importance of arteriogenesis, the biology of the process is poorly understood. Synectin, a gene previously implicated in the regulation of vascular endothelial cell growth factor signaling, 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 knockin mouse line was crossbred with endothelial-specific (Tie2, Cdh5, Pdgfb) and smooth muscle myosin heavy chain-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.

KEYWORDS:

arteries; arteriogenesis; collateral; endothelial cells; receptors; synectin; vascular endothelial growth factor

PMID:
23897694
PMCID:
PMC3865810
DOI:
10.1161/CIRCRESAHA.113.301340
[Indexed for MEDLINE]
Free PMC Article

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