Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling.

Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling.
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DOI:
10.1016/j.cell.2012.10.023
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发表时间:
2012-11-21
期刊:
影响因子:
64.5
通讯作者:
Zhou B
Zhou B
中科院分区:
生物学1区
文献类型:
--
作者:
Wu B;Zhang Z;Lui W;Chen X;Wang Y;Chamberlain AA;Moreno-Rodriguez RA;Markwald RR;O'Rourke BP;Sharp DJ;Zheng D;Lenz J;Baldwin HS;Chang CP;Zhou B

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冠状动脉的起源和发育机制尚不完全清楚。我们通过命运图谱、克隆分析和免疫组织化学表明,心内膜细胞产生冠状动脉内皮。染料追踪、实时成像和组织移植也表明心室心内膜细胞没有终末分化。相反,它们具有血管生成作用并形成冠状动脉内皮网络。心肌 Vegf-a 或心内膜 Vegfr-2 缺失抑制心室心内膜细胞的冠状血管生成和动脉形成。相比之下,谱系和敲除研究表明,心内膜细胞对冠状静脉的贡献很小,其形成独立于心肌到心内膜的 Vegf 信号传导。因此,与目前冠状血管共同来源的观点相反,我们的研究结果表明冠状动脉和静脉具有不同的起源,并由不同的机制形成。这些信息可能有助于开发更好的冠状动脉疾病细胞疗法。
The origins and developmental mechanisms of coronary arteries are incompletely understood. We showed here by fate mapping, clonal analysis and immunohistochemistry that endocardial cells generate the endothelium of coronary arteries. Dye tracking, live imaging, and tissue transplantation also revealed that ventricular endocardial cells are not terminally differentiated; instead, they are angiogenic and form coronary endothelial networks. Myocardial Vegf-a or endocardial Vegfr-2 deletion inhibited coronary angiogenesis and arterial formation by ventricular endocardial cells. In contrast, lineage and knockout studies showed that endocardial cells make a small contribution to the coronary veins, the formation of which is independent of myocardial-to-endocardial Vegf signaling. Thus, contrary to the current view of a common source for the coronary vessels, our findings indicate that the coronary arteries and veins have distinct origins and are formed by different mechanisms. This information may help develop better cell therapies for coronary artery disease.
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