Persoon-Rothert Marion, van der Wees Karlien G C, van der Laarse Arnoud
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Mol Cell Biochem. 2002 Dec;241(1-2):115-24. doi: 10.1023/a:1020860209333.
Apoptosis of cardiac myocytes has been implicated in cardiac dysfunction due to chronic hemodynamic overload. Reports on the role of apoptosis in the transition from hypertrophy to decompensated heart failure are not unequivocal. In this study we analysed the direct relationship between mechanical overload and induction of apoptosis in an in vitro model of cultured heart cells. Cyclic mechanical stretch was applied to cultured neonatal rat ventricular myocytes and fibroblasts. Several indicators of apoptosis were examined, such as morphological features, caspase-3 activity and DNA fragmentation. Mechanical strain did not induce any significant change in these parameters as compared to non-stretched myocytes or fibroblasts. However, administration of staurosporine, a known inducer of apoptosis, induced massive apoptosis in myocytes as well as fibroblasts. We conclude that this in vitro cell model system lacks a direct link between mechanical stretch and apoptosis. The three-dimensional structure-function relationship of myocardial tissue in the intact heart may elicit stretch-induced molecular signaling cascades in a much more complex way than in monolayer cultures of cardiac cells.
心肌细胞凋亡与慢性血流动力学负荷过重导致的心脏功能障碍有关。关于凋亡在从肥大向失代偿性心力衰竭转变过程中的作用的报道并不明确。在本研究中，我们在培养的心脏细胞体外模型中分析了机械负荷与凋亡诱导之间的直接关系。对培养的新生大鼠心室肌细胞和成纤维细胞施加周期性机械拉伸。检测了凋亡的几个指标，如形态学特征、半胱天冬酶-3活性和DNA片段化。与未拉伸的肌细胞或成纤维细胞相比，机械应变并未导致这些参数发生任何显著变化。然而，施用已知的凋亡诱导剂星形孢菌素会在肌细胞和成纤维细胞中诱导大量凋亡。我们得出结论，这个体外细胞模型系统缺乏机械拉伸与凋亡之间的直接联系。完整心脏中心肌组织的三维结构-功能关系可能以比心脏细胞单层培养更为复杂的方式引发拉伸诱导的分子信号级联反应。
