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振荡剪切应力和静水压力调节培养的内皮细胞中的细胞-基质附着蛋白。

Oscillatory shear stress and hydrostatic pressure modulate cell-matrix attachment proteins in cultured endothelial cells.

作者信息

Thoumine O, Nerem R M, Girard P R

机构信息

Bioengineering Center, Georgia Institute of Technology, Atlanta 30332-0230, USA.

出版信息

In Vitro Cell Dev Biol Anim. 1995 Jan;31(1):45-54. doi: 10.1007/BF02631337.

Abstract

Endothelial cells (ECs) may behave as hemodynamic sensors, translating mechanical information from the blood flow into biochemical signals, which may then be transmitted to underlying smooth muscle cells. The extracellular matrix (ECM), which provides adherence and integrity for the endothelium, may serve an important signaling function in vascular diseases such as atherogenesis, which has been shown to be promoted by low and oscillating shear stresses. In this study, confluent bovine aortic ECs (BAECs), were exposed to an oscillatory shear stress or to a hydrostatic pressure of 40 mmHg for time periods of 12 to 48 h. Parallel control cultures were maintained in static condition. Although ECs exposed to hydrostatic pressure or to oscillatory flow had a polygonal morphology similar to that of control cultures, these cells possessed more numerous central stress fibers and exhibited a partial loss of peripheral bands of actin, in comparison to static cells. In EC cultures exposed to oscillatory flow or hydrostatic pressure, extracellular fibronectin (Fn) fibrils were more numerous than in static cultures. Concomitantly, a dramatic clustering of alpha 5 beta 1 Fn receptors and of the focal contact-associated proteins vinculin and talin occurred. Laminin (Ln) and collagen type IV formed a network of thin fibrils in static cultures, which condensed into thicker fibers when BAECs were exposed to oscillatory shear stress or hydrostatic pressure. The ECM-associated levels of Fn and Ln were found to be from 1.5- to 5-fold greater in cultures exposed to oscillatory shear stress or pressure for 12 and 48 h, than in static cultures. The changes in the organization and composition of ECM and focal contacts reported here suggest that ECs exposed to oscillatory shear stress or hydrostatic pressure may have different functional characteristics from cells in static culture, even though ECs in either environment exhibit a similar morphology.

摘要

内皮细胞(ECs)可能充当血液动力学传感器,将来自血流的机械信息转化为生化信号,然后这些信号可能传递给下层的平滑肌细胞。细胞外基质(ECM)为内皮提供黏附性和完整性,在诸如动脉粥样硬化形成等血管疾病中可能发挥重要的信号传导功能,研究表明,低剪切应力和振荡剪切应力可促进动脉粥样硬化的发生。在本研究中,将汇合的牛主动脉内皮细胞(BAECs)暴露于振荡剪切应力或40 mmHg的静水压力下12至48小时。平行的对照培养物保持在静态条件下。尽管暴露于静水压力或振荡流的内皮细胞具有与对照培养物相似的多边形形态,但与静态细胞相比,这些细胞拥有更多的中央应力纤维,并且肌动蛋白外周带部分缺失。在暴露于振荡流或静水压力的内皮细胞培养物中,细胞外纤连蛋白(Fn)原纤维比静态培养物中的更多。同时,α5β1 Fn受体以及粘着斑相关蛋白纽蛋白和踝蛋白发生了显著聚集。层粘连蛋白(Ln)和IV型胶原在静态培养物中形成细纤维网络,当BAECs暴露于振荡剪切应力或静水压力时,这些细纤维会凝聚成更粗的纤维。发现暴露于振荡剪切应力或压力12和48小时的培养物中,与ECM相关的Fn和Ln水平比静态培养物中的高1.5至5倍。此处报道的ECM和粘着斑的组织和组成变化表明,暴露于振荡剪切应力或静水压力的内皮细胞可能具有与静态培养细胞不同的功能特征,尽管在这两种环境中的内皮细胞表现出相似的形态。

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