Biomedical Section, Department of Biological Sciences, University of Hull, Cottingham Road, Hull, HU6 7RX, UK.
Mol Cell Biochem. 2010 Dec;345(1-2):119-30. doi: 10.1007/s11010-010-0565-8. Epub 2010 Aug 22.
Recent evidence has shown that prolonged exposure to exogenous tissue factor (TF) can alter the cellular functions of cardiomyocytes resulting in cardiac dysfunction. The effect of TF may arise from local inflammation within or in the vicinity of the heart. The aim of this study was to investigate the effect of TF on cardiomyocyte proliferation and growth. H9c2 rat cardiomyocytes were exposed to a range of concentrations of recombinant TF (rTF) (1.3-52 ng/ml) for up to 10 days and the outcome on cell proliferation and induction of apoptosis measured. At lower concentrations examined (1.3 ng/ml), rTF had a proliferative influence on the H9c2 cells. In contrast, elevated concentrations of rTF (52 ng/ml) induced cellular apoptosis as indicated by increased caspase-3 activity and nuclear localisation of p53. Moreover, incubation with intermediate concentrations of rTF (13 ng/ml) resulted in an initial increase in proliferation but subsequently, led to cellular apoptosis by day 7 of the incubation. In order to determine if these effects induced hypertrophic cell growth, expression of mechano-growth factor (MGF) was analysed. Incubation of cells with rTF resulted in enhanced expression of MGF particularly at the intermediate concentrations of rTF (13 ng/ml) as well as mean cellular transverse diameter. In addition, there was a rapid increase in the expression of atrial natriuretic factor (ANF) in the cells, on incubation with rTF but diminished rapidly when exposed to higher concentrations of rTF. These data indicate that exposure to increasing concentrations of rTF can accelerate the rate of cardiomyocyte turnover which may ultimately lead to depletion of viable cells within the heart. Moreover, at lower concentrations of rTF, the induction of cell proliferation together with hypertrophic markers indicates that rTF may contribute to the induction and progression of cardiac hypertrophy.
最近的证据表明，长时间接触外源性组织因子 (TF) 会改变心肌细胞的细胞功能，导致心脏功能障碍。TF 的作用可能源于心脏内或附近的局部炎症。本研究旨在探讨 TF 对心肌细胞增殖和生长的影响。将 H9c2 大鼠心肌细胞暴露于一系列浓度的重组 TF(rTF)(1.3-52ng/ml)中长达 10 天，并测量细胞增殖和诱导凋亡的结果。在检查的较低浓度(1.3ng/ml)下，rTF 对 H9c2 细胞具有增殖作用。相比之下，升高浓度的 rTF(52ng/ml)诱导细胞凋亡，这表明 caspase-3 活性增加和 p53 的核定位。此外，中间浓度 rTF(13ng/ml)孵育最初会导致增殖增加，但随后在孵育第 7 天导致细胞凋亡。为了确定这些效应是否诱导了肥大细胞生长，分析了机械生长因子 (MGF) 的表达。rTF 的孵育导致 MGF 的表达增强，尤其是在 rTF 的中间浓度(13ng/ml)以及细胞的平均横向直径。此外，在孵育 rTF 时，细胞内心房利钠因子 (ANF) 的表达迅速增加，但当暴露于更高浓度的 rTF 时迅速减少。这些数据表明，暴露于增加浓度的 rTF 可加速心肌细胞更替的速度，这可能最终导致心脏内存活细胞的耗竭。此外，在 rTF 的较低浓度下，细胞增殖和肥大标志物的诱导表明 rTF 可能有助于心脏肥大的诱导和进展。
