From the Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, New Haven, CT.
Circ Res. 2013 Oct 12;113(9):1076-86. doi: 10.1161/CIRCRESAHA.113.301340. Epub 2013 Jul 29.
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.
We investigated the cell-autonomous effects of a synectin knockout in arterial morphogenesis.
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.
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.
动脉生成是动脉管道形成的过程。促进动脉生成是治疗闭塞性动脉粥样硬化疾病的一种有吸引力的治疗策略。尽管动脉生成具有重要的功能和临床意义，但对其生物学过程知之甚少。连接蛋白是一个先前被认为参与调节血管内皮细胞生长因子信号的基因，为确定各种细胞类型对动脉生成的相对贡献提供了一个独特的机会。
我们研究了动脉形态发生中连接蛋白敲除的细胞自主效应。
将 floxed 连接蛋白敲入小鼠与内皮特异性（Tie2、Cdh5、Pdgfb）和血管平滑肌肌球蛋白重链特异性 Cre 驱动小鼠系杂交，产生细胞类型特异性缺失。内皮细胞而非平滑肌细胞中连接蛋白表达的缺失导致发育性动脉形态发生缺陷（动脉树较小、动脉分支和侧支减少）和成年小鼠的动脉生成受损。
连接蛋白以内皮细胞自主的方式调节发育和成年动脉生成。这些发现首次表明内皮细胞是发育和成年动脉生成的核心，并为未来研究该过程中涉及的因素提供了模型。
