Neuregulin in cardiovascular development and disease.
Neuregulin in cardiovascular development and disease.
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DOI：
10.1161/circresaha.112.267286
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发表时间：
2012-10-26
影响因子：
20.1
通讯作者：
Sawyer DB
中科院分区：
文献类型：
--
作者：
Odiete O;Hill MF;Sawyer DB
对转基因小鼠的研究表明，NeuRegin-1(NRG-1)以及红细胞白血病病毒癌基因同源基因(ErbB)2、3和4受体酪氨酸激酶是心血管发育的多个方面所必需的。这些观察刺激了体外和体内的动物研究，暗示NRG-1/ErbB信号在整个生命过程中对心脏细胞生物学的调节。ErbB2靶向癌症治疗的心血管效应在人类中提供了证据，证明ErbB信号在维持心脏功能方面发挥作用。这些和其他研究提出了一个概念性模型，在该模型中，NRG-1/ErbB信号的一个关键功能是通过激活调节组织可塑性的细胞内激酶级联反应来调节心脏对生理和病理刺激的适应。最近的工作涉及NRG-1/ErbB信号在心血管生物学的多个方面的调节，包括血管生成、血压和骨骼肌对运动的反应。重组NRG-1作为一种潜在的治疗心力衰竭的药物的潜力已经在动物模型中得到证实，目前正在进行临床研究。在人血清和血浆中发现NRG-1，并与一些临床参数相关，提示它可能作为预后的指标。在这篇综述中，我们汇集了关于NRG-1及其在心血管发育和疾病中的重要性的日益增长的文献。
Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease.