CCBE1 is Required for Coronary Vessel Development and Proper Coronary Artery Stem Formation in the Mouse Heart

被引:17
作者
Bonet, Fernando [1 ]
Pereira, Paulo N. G. [1 ]
Bover, Oriol [1 ]
Marques, Sara [1 ]
Inacio, Jose M. [1 ]
Belo, Jose A. [1 ]
机构
[1] Univ Nova Lisboa, Fac Ciencias Med, NOVA Med Sch, Stem Cells & Dev Lab,CEDOC,Chron Dis Res Ctr, Lisbon, Portugal
关键词
CCBE1; coronary vasculature; heart development; epicardium; sinus venosus; VEGF-C; ENDOTHELIAL-CELLS; FORM; LYMPHANGIOGENESIS; ORIGIN; VASCULATURE; MUTATIONS; DYSPLASIA; ANOMALIES;
D O I
10.1002/dvdy.24670
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Background: Proper coronary vasculature development is essential for late-embryonic and adult heart function. The developmental regulation of coronary embryogenesis is complex and includes the coordinated activity of multiple signaling pathways. CCBE1 plays an important role during lymphangiogenesis, enhancing VEGF-C signaling, which is also required for coronary vasculature formation. However, whether CCBE1 plays a similar role during coronary vasculature development is still unknown. Here, we investigate the coronary vasculature development in Ccbe1 mutant embryos. Results: We show that Ccbe1 is expressed in the epicardium, like Vegf-c, and also in the sinus venosus (SV) at the stages of its contribution to coronary vasculature formation. We also report that absence of CCBE1 in cardiac tissue inhibited coronary growth that sprouts from the SV endocardium at the dorsal cardiac wall. This disruption of coronary formation correlates with abnormal processing of VEGF-C propeptides, suggesting VEGF-C-dependent signaling alteration. Moreover, Ccbe1 loss-of-function leads to the development of defective dorsal and ventral intramyocardial vessels. We also demonstrate that Ccbe1 mutants display delayed and mispatterned coronary artery (CA) stem formation. Conclusions: CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. (c) 2018 Wiley Periodicals, Inc.
引用
收藏
页码:1135 / 1145
页数:11
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