期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 30, 期 8, 页码 1569-1575出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.110.209163
关键词
adhesion molecules; angiogenesis; ischemia; peripheral arterial disease; vascular biology
资金
- Ministere de l'Enseignement Superieur et de la Recherche
- Centre National de la Recherche Scientifique
Objective-Alpha6 integrin subunit (alpha 6) expression is increased by proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor. This increase correlates with enhanced in vitro tube formation by endothelial cells and their progenitors called Endothelial Colony-Forming Cells (ECFCs). We thus studied the role of alpha 6 in vasculogenesis induced by human ECFCs, in a mouse model of hindlimb ischemia. Methods and Results-We used small interfering RNA (siRNA) to inhibit alpha 6 expression on the surface of ECFCs. For in vivo studies, human ECFCs were injected intravenously into a nude mouse model of unilateral hind limb ischemia. Transfection with siRNA alpha 6 abrogated neovessel formation and reperfusion of the ischemic hind limb induced by ECFCs (P<0.01 and P<0.001, respectively). It also inhibited ECFC incorporation into the vasculature of the ischemic muscle (P<0.001). In vitro, siRNA alpha 6 inhibited ECFC adhesion (P<0.01), pseudotube formation on Matrigel, migration, and AKT phosphorylation (P<0.0001), with no effect on cell proliferation or apoptosis. Conclusion-alpha 6 Expression is required for ECFC migration, adhesion, recruitment at the site of ischemia, and the promotion of the postischemic vascular repair. Thus, we have demonstrated a major role of alpha 6 in the proangiogenic properties of ECFCs. (Arterioscler Thromb Vasc Biol. 2010;30:1569-1575.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据