Department of Chemical Engineering, McGill University, 3610 University Street, Montréal, QC, H3A 0C5, Canada.
Montreal Heart Institute, 5000 Rue Bélanger, Montréal, QC, H1T 1C8, Canada.
Ann Biomed Eng. 2017 Sep;45(9):2234-2243. doi: 10.1007/s10439-017-1846-0. Epub 2017 May 4.
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.
已知血流动力能够诱导内皮细胞（EC）产生炎症表型。EC 糖萼（GCX）是一种动态结构，可响应不同的刺激进行调节，并被假设为壁切应力（WSS）机械转导的重要贡献者。在这项工作中，我们使用具有 50%不对称狭窄的三维体外 EC 培养模型来研究 MMP 活性增加导致的 GCX 在 WSS 梯度区域的降解，以及这种降解如何产生促炎环境。实验表明，在 50%不对称狭窄产生的 WSSG 区域观察到 GCX 降解。此外，抑制 MMP 活性可消除这种区域降解。GCX 的完整性改变了 EC 形态向流动的延伸和白细胞黏附模式。这些结果有助于加强以下假说，即 EC GCX 参与血流动力的机械转导，并且在 WSSG 区域 GCX 受 MMP 活性调节。
