Mechanical and neurohumoral regulation of adult cardiocyte growth.
Mechanical and neurohumoral regulation of adult cardiocyte growth.
复制标题
成人心肌细胞生长的机械和神经体液调节。
DOI：
10.1111/j.1749-6632.1995.tb17420.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Clark,WA
中科院分区：
文献类型：
--
作者：
Decker,RS;Decker,ML;Behnke-Barclay,MM;Janes,DM;Clark,WA
成人心肌细胞的培养为直接探索调节成熟心肌细胞生长的潜在调控途径提供了机会。1当使用整个动物时，识别介导成年心肌细胞生长的亚细胞事件和信号转导通路在引发心肌肥大的应激反应中是有限的，因为在活体内解开由影响引起的原因通常因心脏的细胞异质性和完整心肌内可能存在的神经体液相互作用而复杂化。2-4神经递质释放的变化、血浆激素水平的波动以及随之而来的血流动力学负荷的变化，使得充其量很难准确确定假设的化学和物理信号如何调节体内的细胞生长。培养的心肌细胞提供了一种实验范式，可以更明确地识别和表征在特定和相对简单的环境中控制心肌细胞生长的可能途径。然而，在考虑使用这种模式系统之前，应该考虑几点注意事项。在大多数情况下，二维成人心肌细胞培养的产生最大限度地减少了心肌细胞与非心肌细胞的相互作用，改变了重建的“体外心肌”的几何形状，并改变了支持心肌细胞生长的细胞外环境(即培养介质和细胞外基质)。用于研究的心脏细胞的来源(即，它们是来自发育中的心脏还是成人心脏)也值得特别考虑。从胚胎、新生儿或成人心脏中分离的心肌细胞具有独特的特性，使它们每一个都有助于研究心脏生长和发育的特定方面。胚胎心脏细胞可能是探索心源性决定的理想细胞，而新生儿心肌细胞则非常适合研究出生后心肌的生长。相反，成人心肌细胞可以有效地用于探索生理性肥厚的调节，或许还有病理生理学肥厚。这份报告的主要焦点将是比较和对比机械负荷和神经体液激活如何调节成年心肌细胞的生长，并在可能的情况下确定
Culture of adult cardiac myocytes provides an opportunity to directly explore potential regulatory pathways that modulate the growth of the mature heart cell. 1 Identifying subcellular events and signal transduction pathways that mediate the growth of the adult cardiac myocyte in response to stresses that provoke cardiac hypertrophy is limited when whole animals are employed, because unraveling" cause from effect" in vivo is often complicated by the cellular heterogeneity of the heart and the likely neurohumoral interactions that exist within the intact myocardium. 2-4 Changes in neurotransmitter release, fluctuating plasma hormone levels and attendant alterations in hemodynamic load make it difficult, at best, to precisely determine how postulated chemical and physical signals regulate cellular growth in vivo. Cultured cardiac myocytes provide an experimental paradigm to more definitively identify and characterize putative pathways that control cardiocyte growth in a defined and relatively uncomplicated environment. There are several caveats, however, that should be considered before contemplating the use of such a model system. The production of two-dimensional adult cardiocyte cultures minimizes, in most instances, myocyte-nonmyocyte interactions, alters the geometry of this reestablished" in vitro myocardium" and modifies the extracellular environment (ie, the culture medium and extracellular matrix) that supports cardiocyte growth. The source of the heart cells employed for study (ie, are they derived from developing or adult heart) also deserves special consideration. Cardiac myocytes isolated from embryonic, neonatal or adult hearts possess unique properties that make each of them useful for the study of specific aspects of cardiac growth and development. Embryonic heart cells are, perhaps, ideal for exploring cardiogenic determination, while neonatal myocytes are well suited for investigating postnatal myocardial growth. In contrast, adult cardiocytes can be usefully employed to explore the regulation of physiologic and, perhaps, pathophysiologic hypertrophy. The principal focus of this report will be to compare and contrast how mechanical loading and neurohumoral activation modulate the growth of adult cardiac myocytes and, where possible, to determine whether the