Stenosis Hemodynamics Disrupt the Endothelial Cell Glycocalyx by MMP Activity Creating a Proinflammatory Environment
Stenosis Hemodynamics Disrupt the Endothelial Cell Glycocalyx by MMP Activity Creating a Proinflammatory Environment
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DOI：
10.1007/s10439-017-1846-0
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发表时间：
2017-09-01
影响因子：
3.8
通讯作者：
Leask, Richard L.
中科院分区：
文献类型：
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作者：
Cooper, S.;McDonald, K.;Leask, Richard L.
已知血流动力学能够诱导内皮细胞（EC）中的炎性表型。EC糖萼（GCX）是一种动态结构，其响应于不同的刺激而被调节，并且被假设为壁切应力（WSS）的机械转导的重要贡献者。在这项工作中，我们使用了三维体外EC培养模型与50%的不对称狭窄，以研究GCX的降解增加的基质金属蛋白酶（MMP）的活性在WSS梯度的区域，以及如何这种降解可能会创建一个促炎环境。实验表明，GCX降解中观察到的区域WSSG创建的50%的不对称狭窄。此外，抑制MMP活性消除了这种区域性降解。GCX的完整性改变了EC的形态伸长流动和白细胞粘附模式。这些结果有助于加强假设EC GCX是参与mechanodendon的血流动力学力量和GCX的MMP活性的WSSGs地区的调节。
Hemodynamic forces are known to be able to induce an inflammatory phenotype in endothelial cells (ECs). The EC glycocalyx (GCX) is a dynamic structure which is regulated in response to different stimuli and hypothesized as an important contributor to the mechanotransduction of wall shear stresses (WSS). In this work, we used a three dimensional in vitro EC culture model with a 50% asymmetric stenosis to investigate degradation of the GCX by increased matrix metalloproteinase (MMP) activity in regions of WSS gradients and how this degradation might create a proinflammatory environment. Experiments showed GCX degradation was observed in regions of WSSGs created by a 50% asymmetric stenosis. Furthermore, inhibition of MMP activity abolished this regional degradation. The integrity of the GCX altered EC morphological elongation to flow and leukocyte adhesion patterns. These results help strengthen the hypothesis that the EC GCX is involved in the mechanotransduction of hemodynamic forces and that the GCX is regulated by MMP activity in regions of WSSGs.