The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development
The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development
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DOI：
10.1101/gad.12.21.3320
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发表时间：
1998-11-01
影响因子：
10.5
通讯作者：
McKnight, SL
中科院分区：
文献类型：
--
作者：
Tian, H;Hammer, RE;McKnight, SL
缺乏缺氧诱导转录因子EPAS1的小鼠在妊娠中期死亡。尽管循环系统的形态发育正常，epas1缺陷小鼠表现出明显的心动过缓。除了血管内皮外，EPAS1在哺乳动物胚胎中儿茶酚胺产生的主要来源Zuckerkandl （OZ）器官中也有大量表达。epas1缺陷胚胎含有大量降低的儿茶酚胺水平。妊娠中期的致命性是通过给孕妇服用儿茶酚胺前体DOPS来挽救的。我们推测，EPAS1在妊娠中期在OZ中表达，并将该信号转化为基因表达模式的改变，从而导致循环儿茶酚胺水平的增加和心脏功能的正常。
Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to the vascular endothelium, EPAS1 is expressed intensively in the organ of Zuckerkandl (OZ), the principle source of catecholamine production in mammalian embryos. EPAS1-deficient embryos contained substantially reduced catecholamine levels. Mid-gestational lethality was rescued by administration of the catecholamine precursor DOPS to pregnant females. We hypothesize that EPAS1 expressed in the OZ senses hypoxia during midgestational development and translates this signal into an altered pattern of gene expression, leading to increases in circulating catecholamine levels and proper cardiac function.