Gonzales R S, Wick T M
School of Chemical Engineering, Georgia Institute of Technology, Atlanta 30332-0100, USA.
Ann Biomed Eng. 1996 May-Jun;24(3):382-93. doi: 10.1007/BF02660887.
Hemodynamic shear stress is hypothesized to contribute to the localization of atherosclerotic plaques to certain arterial sites. Monocyte recruitment to these sites is an early event in artherogenesis. To determine the possible mechanisms by which shear stress modulates monocyte adhesion in vivo, studies of human monocytic cell adherence to endothelium were conducted under different shear conditions in a parallel-plate flow chamber. The number of monocytes capable of developing firm adhesive contacts with endothelium decreased as shear stress-induced drag forces increased over the range of 0.5 to 30 dynes/cm2. The number of adherent monocytic cells at a given shear stress was highly dependent on the activation state of the endothelium. To test the direct effect of shear stress on endothelial cell adhesivity, endothelial cells were presheared for 2 to 6 hr at 2, 10, or 30 dynes/cm2, and monocytic cell adherence was quantified at 1 dyne/cm2. Adherence increased 330% or 370% when endothelial cells were presheared for 2 hr at 2 or 10 dynes/cm2, respectively, as compared to unsheared endothelium. In contrast, when endothelial cells were presheared at 30 dynes/cm2, monocytic cell adherence at 1 dyne/cm2 was not significantly different from unsheared controls. Increased monocytic cell adherence to presheared endothelium was via a vascular cell adhesion molecule 1 (VCAM-1)/alpha(4) beta(1) mechanism, and enzyme-linked immunosorbent assay studies showed that preshearing at 2 dynes/cm2 for 2 hr increased endothelial VCAM-1 expression by 38%. These data demonstrate that low levels of shear stress induce endothelial VCAM-1 expression and increase monocytic cell adherence via a VCAM-1/alpha 4 beta 1 mechanism. Thus, shear stress can modulate monocyte adherence to vascular endothelium through drag forces that affect the establishment and maintenance of adhesive bonds and by directly modulating the expression of endothelial VCAM-1. This dual effect of shear stress produces the most favorable conditions for adhesion at low-shear regions, where drag forces are low and induction of VCAM-1 is likely. The preferential adherence of monocytes to these regions may contribute to the localization of atherosclerotic plaques to low-shear regions of the arterial circulation in vivo.
血流动力学剪切应力被认为与动脉粥样硬化斑块在某些动脉部位的定位有关。单核细胞募集到这些部位是动脉粥样硬化发生的早期事件。为了确定剪切应力在体内调节单核细胞黏附的可能机制，在平行平板流动腔中，于不同剪切条件下对人单核细胞与内皮细胞的黏附进行了研究。随着剪切应力诱导的拖曳力在0.5至30达因/平方厘米范围内增加，能够与内皮细胞形成牢固黏附接触的单核细胞数量减少。在给定剪切应力下，黏附的单核细胞数量高度依赖于内皮细胞的激活状态。为了测试剪切应力对内皮细胞黏附性的直接影响，将内皮细胞在2、10或30达因/平方厘米的剪切应力下预剪切2至6小时，然后在1达因/平方厘米下对单核细胞黏附进行定量。与未预剪切的内皮细胞相比，当内皮细胞在2或10达因/平方厘米下预剪切2小时时，黏附分别增加了330%或370%。相比之下，当内皮细胞在30达因/平方厘米下预剪切时，1达因/平方厘米下的单核细胞黏附与未预剪切的对照组无显著差异。单核细胞对预剪切内皮细胞的黏附增加是通过血管细胞黏附分子1（VCAM-1）/α4β1机制实现的，酶联免疫吸附测定研究表明，在2达因/平方厘米下预剪切2小时可使内皮细胞VCAM-1表达增加38%。这些数据表明，低水平的剪切应力通过VCAM-1/α4β1机制诱导内皮细胞VCAM-1表达并增加单核细胞黏附。因此，剪切应力可通过影响黏附键的建立和维持的拖曳力以及直接调节内皮细胞VCAM-1的表达来调节单核细胞对血管内皮的黏附。剪切应力的这种双重作用在低剪切区域产生了最有利于黏附的条件，在这些区域拖曳力低且可能诱导VCAM-1。单核细胞对这些区域的优先黏附可能有助于动脉粥样硬化斑块在体内动脉循环低剪切区域的定位。
