The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis
The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis
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DOI：
10.1242/dev.113639
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发表时间：
2014-12-01
期刊：
影响因子：
4.6
通讯作者：
Red-Horse, Kristy
中科院分区：
文献类型：
--
作者：
Chen, Heidi I.;Sharma, Bikram;Red-Horse, Kristy
鉴定冠状动脉祖细胞及其发育途径可以激发心脏病的新再生治疗。冠状动脉血管的多种来源已被提出，包括静脉窦（SV），内膜和心外膜，但他们的相对贡献冠状动脉循环和调节其发展的分子机制知之甚少。我们创建了ApjCreER小鼠系作为谱系追踪工具，将SV衍生的血管映射到心脏上，并将所得谱系模式与冠状动脉循环的内膜和心外膜贡献进行比较。数据显示冠状动脉的发展有明显的区室化。ApjCreER追踪的血管构成了心脏背侧和外侧的大量动脉、毛细血管和静脉。相比之下，未追踪的血管主要分布在腹侧和室间隔的中线，这些血管群主要来自内膜。心外膜引起了一个小部分的血管相对均匀地分布在整个心室壁。背侧（SV衍生）和腹侧（心内膜衍生）冠状血管的发展，以响应不同的生长信号。VEGFC在心外膜中表达，它的缺失显著抑制了背侧和侧冠状动脉的生长，但腹侧的血管不受影响。我们建议，互补的SV衍生和心内膜衍生的迁移路线联合起来形成冠状动脉血管系统，前者需要VEGFC，揭示其作为血液内皮发育的组织特异性介质的作用。
Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of coronary vessels have been proposed, including the sinus venosus (SV), endocardium and proepicardium, but their relative contributions to the coronary circulation and the molecular mechanisms regulating their development are poorly understood. We created an ApjCreER mouse line as a lineage-tracing tool to map SV-derived vessels onto the heart and compared the resulting lineage pattern with endocardial and proepicardial contributions to the coronary circulation. The data showed a striking compartmentalization to coronary development. ApjCreER-traced vessels contributed to a large number of arteries, capillaries and veins on the dorsal and lateral sides of the heart. By contrast, untraced vessels predominated in the midline of the ventral aspect and ventricular septum, which are vessel populations primarily derived from the endocardium. The proepicardium gave rise to a smaller fraction of vessels spaced relatively uniformly throughout the ventricular walls. Dorsal (SV-derived) and ventral (endocardial-derived) coronary vessels developed in response to different growth signals. The absence of VEGFC, which is expressed in the epicardium, dramatically inhibited dorsal and lateral coronary growth but left vessels on the ventral side unaffected. We propose that complementary SV-derived and endocardial-derived migratory routes unite to form the coronary vasculature and that the former requires VEGFC, revealing its role as a tissue-specific mediator of blood endothelial development.