c-Myc is required for proper coronary vascular formation via cell- and gene-specific signaling.
c-Myc is required for proper coronary vascular formation via cell- and gene-specific signaling.
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c-Myc 是通过细胞和基因特异性信号传导正确形成冠状血管所必需的。
DOI:
10.1161/atvbaha.111.244590
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发表时间:
2012
期刊:
影响因子:
--
通讯作者:
Baudino,TroyA
中科院分区:
文献类型:
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作者:
Souders,ColbyA;Bowers,StephanieLK;Banerjee,Indroneal;Fuseler,JohnW;Demieville,JenniferL;Baudino,TroyA
ObjectiveAlthough significant research has detailed angiogenesis during development and cancer, little is known about cardiac angiogenesis, yet it is critical for survival following pathological insult. The transcription factor c-Myc is a target of anticancer therapies because of its mitogenic and proangiogenic induction. In the current study, we investigate its role in cardiac angiogenesis in a cell-dependent and gene-specific context.Methods and ResultsAngiogenesis assays using c-Myc-deficient cardiac endothelial cells and fibroblasts demonstrate that c-Myc is essential to vessel formation, and fibroblast-mediated vessel formation is dependent on c-Myc expression in fibroblasts. Gene analyses revealed that c-Myc–mediated gene expression is unique in cardiac angiogenesis and varies in a cell-dependent manner. In vitro 3-dimensional cultures demonstrated c-Myc’s role in the expression of secreted angiogenic factors, while also providing evidence for c-Myc–mediated cell–cell interactions. Additional in vivo vascular analyses support c-Myc’s critical role in capillary formation and vessel patterning during development and also in response to a pathological stimulus where its expression in myocytes is required for angiogenic remodeling.ConclusionThese data demonstrate that proper c-Myc expression in cardiac fibroblasts and myocytes is essential to cardiac angiogenesis. These results have the potential for novel therapeutic applications involving the angiogenic response during cardiac remodeling.