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机械应力与人类主动脉平滑肌细胞增殖

Mechanical stress and human aortic smooth muscle cell proliferation.

作者信息

Kawaguchi H, Ozaki T, Murakami T, Iizuka K

机构信息

Laboratory Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Exp Clin Cardiol. 2001 Spring;6(1):24-8.

Abstract

BACKGROUND

Mechanical forces related to pressure and flow are important for cell hypertrophy and proliferation.

OBJECTIVE

To test the hypothesis that mechanosensors are present that are sensitive solely to pure atmospheric pressure in the absence of shear and tensile stresses.

METHODS AND RESULTS

A pressure-loading apparatus was set up to examine the effects of atmospheric pressure on human aortic smooth muscle cells. Pressure application of 140 to 180 mmHg produced DNA synthesis in a pressure-dependent manner. In contrast, pressure of 120 mmHg or less produced no significant change. Pertussis toxin completely inhibited the pressure-induced increase of DNA synthesis under the high pressure of 200 mmHg. The activities of both extracellular signal-related kinase and c-Jun N-terminal kinase, but not of p38, were stimulated by a pressure of more than 160 mmHg.

CONCLUSION

These data suggest that human aortic smooth muscle cells have a mechanosensing cellular switch for DNA synthesis that is sensitive to pure atmospheric pressure, and that the molecular switch is activated by pressure of more than 140 mmHg. The activation mechanism consists of pertussis toxin-sensitive and -insensitive pathways, and the former is activated by high pure pressure.

摘要

背景

与压力和血流相关的机械力对细胞肥大和增殖很重要。

目的

验证在不存在剪切应力和拉伸应力的情况下,存在仅对纯大气压力敏感的机械传感器这一假设。

方法与结果

建立压力加载装置以检测大气压力对人主动脉平滑肌细胞的影响。施加140至180 mmHg的压力可使DNA合成呈压力依赖性增加。相比之下,120 mmHg或更低的压力未产生显著变化。百日咳毒素完全抑制了200 mmHg高压下压力诱导的DNA合成增加。细胞外信号调节激酶和c-Jun氨基末端激酶的活性在压力超过160 mmHg时受到刺激,但p38的活性未受刺激。

结论

这些数据表明,人主动脉平滑肌细胞具有对纯大气压力敏感的用于DNA合成的机械传感细胞开关,且该分子开关在压力超过140 mmHg时被激活。激活机制包括百日咳毒素敏感和不敏感途径,前者由高纯度压力激活。

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