WALL SHEAR-STRESS RATHER THAN SHEAR RATE REGULATES CYTOPLASMIC CA++ RESPONSES TO FLOW IN VASCULAR ENDOTHELIAL-CELLS
WALL SHEAR-STRESS RATHER THAN SHEAR RATE REGULATES CYTOPLASMIC CA++ RESPONSES TO FLOW IN VASCULAR ENDOTHELIAL-CELLS
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DOI：
10.1006/bbrc.1993.1108
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发表时间：
1993-02-15
影响因子：
3.1
通讯作者：
KAMIYA, A
中科院分区：
文献类型：
--
作者：
ANDO, J;OHTSUKA, A;KAMIYA, A
近年来的研究表明，血管内皮细胞（vascular endothelial cell，EC）可以感知其表面的流速，并根据这一信息调节自身的形态和功能，同时也调节周围平滑肌和其他组织的形态和功能。现在讨论的是以下哪种机制实际上启动了EC对流动的信号处理反应：由于流动导向的壁剪切应力（τ）引起的细胞的机械剪切变形，或由壁剪切速率（γ）调节的血管活性激动剂在细胞表面的扩散积聚，或两者兼而有之。为了确定每种机制的相对重要性，我们检测了在Ca++动员激动剂ATP存在下培养的EC中细胞质游离Ca++浓度（[Ca++]i）的定量变化，即，灌注两种具有不同粘度（μ）的缓冲液后，内部信号系统的第二信使响应，将这些因素联系起来，如τ = μγ。用Fura-2对EC进行体外荧光分光光度测定，结果表明：EC的[Ca++] i随剪切速率的增加而增加，但粘度越高，增加的程度越大;在相同的剪切应力下，无论剪切速率和粘度如何，EC的[Ca++] i值几乎相同。这种定量的一对一之间的关系的剪切应力和第二信使的反应表明，壁剪切应力，而不是壁剪切速率是主要的物理因素引起EC响应流。
Recent evidence suggests that the vascular endothelial cell (EC) can sense the flow-rate over its surface and according to the information, regulates not only its own morphology and functions but also those of the surrounding smooth muscle and other tissues. There is now a discussion over which of the following mechanisms actually initiates the signal-transacting response of EC against flow: the mechanical shear deformation of the cell due to flow-oriented wall shear stress (τ), or the diffusional accumulation of vasoactive agonists on the cell surface modulated by wall shear rate (γ) or both. To identify the relative importance of each mechanism, we examined quantitative changes in the cytoplasmic free Ca++concentration ([Ca++]i) in cultured EC in the presence of the Ca++mobilizing agonist ATP, i.e., a second messenger response of the internal signalling system, following the perfusion of two buffers with different viscosities (μ), which relates these factors as τ = μγ. The results of in vitro fluorescence photometry in EC with Fura-2 showed that the [Ca++i] level was enhanced with increase in the shear rate but to a greater extent with higher viscosity, and that the [Ca++]ilevels at the same calculated level of shear stress were virtually identical, regardless of difference in shear rate and viscosity. This quantitative one-to-one relationship between the shear stress and the second messenger response suggests that wall shear stress rather than wall shear rate is the principal physical factor eliciting EC responses to flow.