Fisher S A, Langille B L, Srivastava D
Departments of Medicine and Physiology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA.
Circ Res. 2000 Nov 10;87(10):856-64. doi: 10.1161/01.res.87.10.856.
Morphogenesis and developmental remodeling of cardiovascular tissues involve coordinated regulation of cell proliferation and apoptosis. In the heart, clear evidence points toward focal apoptosis as a contributor to development of the embryonic outflow tract, cardiac valves, conducting system, and the developing coronary vasculature. Apoptosis in the heart is likely regulated by survival and death signals that are also present in many other tissues. Cell type-specific regulation may be superimposed on general cell death/survival machinery through tissue-specific transcriptional pathways. In the vasculature, apoptosis almost certainly contributes to developmental vessel regression, and it is of proven importance in remodeling of arterial structure in response to local changes in hemodynamics. Physical forces, growth factors, and extracellular matrix drive vascular cell survival pathways, and considerable evidence points to local nitric oxide production as an important but complex regulator of vascular cell death. In both the heart and vasculature, progress has been impeded by inadequate information concerning the incidence of apoptosis, its relative importance compared with the diverse cell behaviors that remodel developing tissues, and by our primitive knowledge concerning regulation of cell death in these tissues. However, tools are now available to better understand apoptosis in normal and abnormal development of cardiovascular structures, and a framework has been established that should lead to considerable progress in the coming years.
心血管组织的形态发生和发育重塑涉及细胞增殖和凋亡的协调调控。在心脏中，明确的证据表明局部凋亡是胚胎流出道、心脏瓣膜、传导系统以及发育中的冠状血管发育的一个促成因素。心脏中的凋亡可能受许多其他组织中也存在的存活和死亡信号调控。细胞类型特异性调控可能通过组织特异性转录途径叠加在一般的细胞死亡/存活机制之上。在脉管系统中，凋亡几乎肯定有助于发育过程中血管的消退，并且在响应局部血流动力学变化时动脉结构重塑中已证明其重要性。物理力、生长因子和细胞外基质驱动血管细胞存活途径，大量证据表明局部一氧化氮的产生是血管细胞死亡的重要但复杂的调节因子。在心脏和脉管系统中，由于关于凋亡发生率的信息不足、与重塑发育中组织的多种细胞行为相比其相对重要性以及我们对这些组织中细胞死亡调控的原始认识，进展受到阻碍。然而，现在有工具可用于更好地理解心血管结构正常和异常发育中的凋亡，并且已经建立了一个框架，有望在未来几年取得重大进展。
