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首页> 外文期刊>Mechanisms of Development >Transcription factor CHF1/Hey2 regulates coronary vascular maturation
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Transcription factor CHF1/Hey2 regulates coronary vascular maturation

机译：转录因子CHF1 / Hey2调节冠状血管成熟

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The transcription factor CHF1/Hey2 has been implicated in a variety of cardiovascular developmental abnormalities including ventricular septal defect, deformed valves and cardiomyopathy. To date, its role in coronary vascular development remains unknown. We have found that KO mice developed coronary vascular abnormalities accompanied by a thin compact ventricular myocardium but grossly normal epicardial and subepicardial layers. The coronary vascular anomalies included dysmorphic large vessels and abnormal vascular structures at E15.5 and reduced recruitment of vascular smooth muscle cells into the coronary arteries at E18.5. In E18.5 KO hearts, the abnormal coronary veins demonstrated reduced expression of markers for vein identity. Whole-mount PECAM staining of the E18.5 KO hearts indicated that EphB4 negative vein networks were increased in the surface layers of the myocardium compared to those of the controls. CHF1/Hey2 was not expressed in the epicardium in vivo, and cultured epicardium-derived cells isolated from E12.5 wild-type mice showed no CHF1/Hey2 expression. KO mice with a myocardially expressed CHF1/Hey2 transgene partially rescued the vascular phenotypes. Quantitative RT-PCR analysis demonstrated that PDGF and Angiopoietin/Tie2 signaling pathways are altered in E12.5 KO hearts. Taken together, global CHF1/Hey2 deficiency caused impaired vascular formation, the reduced recruitment of vascular smooth muscle cells into coronary arteries and abnormally remodeled vein networks. These findings suggest that CHF1/Hey2 regulates the later steps of coronary vascular development in both a myocardial-dependent, non-cell autonomous fashion and likely a vascular cell-specific effect as well
机译：转录因子CHF1 / Hey2与多种心血管发育异常有关，包括室间隔缺损，瓣膜变形和心肌病。迄今为止，其在冠状血管发育中的作用仍然未知。我们发现KO小鼠出现冠状血管异常，伴有薄而紧凑的心室心肌，但心外膜和心外膜层基本正常。冠状血管异常包括E15.5处畸形大血管和异常血管结构，E18.5处血管平滑肌细胞向冠状动脉的募集减少。在E18.5 KO心脏中，异常冠状静脉显示出用于静脉身份的标记物表达减少。对E18.5 KO心脏进行的全装载PECAM染色表明，与对照组相比，EphB4负静脉网络在心肌表面层中增加。 CHF1 / Hey2在体内的心外膜中不表达，并且从E12.5野生型小鼠分离的培养的心外膜衍生细胞未显示CHF1 / Hey2的表达。具有心肌表达的CHF1 / Hey2转基因的KO小鼠部分挽救了血管表型。定量RT-PCR分析表明PDGF和血管生成素/ Tie2信号通路在E12.5 KO心脏中被改变。总体而言，全球性CHF1 / Hey2缺乏症导致血管形成受损，血管平滑肌细胞向冠状动脉的募集减少以及异常重构的静脉网络。这些发现表明，CHF1 / Hey2以心肌依赖性，非细胞自主方式以及可能具有血管细胞特异性作用的方式调节冠状血管发育的后期步骤。

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