Epicardium-derived cells are important for correct development of the Purkinje fibers in the avian heart
Epicardium-derived cells are important for correct development of the Purkinje fibers in the avian heart
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DOI：
10.1002/ar.a.20398
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发表时间：
2006-12-01
期刊：
影响因子：
--
通讯作者：
Gittenberger-De Groot, Adriana C.
中科院分区：
文献类型：
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作者：
Eralp, Ismail;Lie-Venema, Heleen;Gittenberger-De Groot, Adriana C.
在胚胎发育过程中，心外膜器官（PEO）在心脏表面生长形成心外膜。在上皮-间充质转化后，心外膜衍生细胞（EPDC）迁移到心脏中并有助于冠状动脉、瓣膜和心肌的发育。外周浦肯野纤维网从心室肌中分化的心肌细胞发育而来。感兴趣的迁移EPDCs和浦肯野纤维分化在禽心脏的最终目的地之间的密切空间关系，也就是说，周围的冠状动脉和在subendoorphins网站，我们研究是否抑制心外膜生长会干扰心肌细胞分化成浦肯野纤维。为此，心外膜发育被机械地用膜抑制，或遗传地，通过用影响Ets转录因子水平的反义逆转录病毒载体抑制心外膜上皮向间充质转化（n = 4，HH 39 -41）。在这两种心外膜抑制模型中，我们通过EAP-300免疫组织化学评价了浦肯野纤维的发育，发现对EPDC发育的抑制导致浦肯野纤维的形态学异常分化。浦肯野纤维发育不全观察到动脉周围和动脉内膜下的位置。此外，细胞形态异常，不排列在有序的浦肯野纤维。我们的结论是，EPDCs是浦肯野纤维分化的工具，我们假设，他们直接与内皮细胞和内皮细胞的外周传导系统的发展。
During embryonic development, the proepicardial organ (PEO) grows out over the heart surface to form the epicardium. Following epithelial-mesenchymal transformation, epicardium-derived cells (EPDCs) migrate into the heart and contribute to the developing coronary arteries, to the valves, and to the myocardium. The peripheral Purkinje fiber network develops from differentiating cardiomyocytes in the ventricular myocardium. Intrigued by the close spatial relationship between the final destinations of migrating EPDCs and Purkinje fiber differentiation in the avian heart, that is, surrounding the coronary arteries and at subendocardial sites, we investigated whether inhibition of epicardial outgrowth would disturb cardiomyocyte differentiation into Purkinje fibers. To this end, epicardial development was inhibited mechanically with a membrane, or genetically, by suppressing epicardial epithelial-to-mesenchymal transformation with antisense retroviral vectors affecting Ets transcription factor levels (n = 4, HH39-41). In both epicardial inhibition models, we evaluated Purkinje fiber development by EAP-300 immunohistochemistry and found that restraints on EPDC development resulted in morphologically aberrant differentiation of Purkinje fibers. Purkinje fiber hypoplasia was observed both periarterially and at subendocardial positions. Furthermore, the cells were morphologically abnormal and not aligned in orderly Purkinje fibers. We conclude that EPDCs are instrumental in Purkinje fiber differentiation, and we hypothesize that they cooperate directly with endothelial and endocardial cells in the development of the peripheral conduction system.