Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan; Department of Ocular Tissue Engineering, Asahikawa Medical University, Asahikawa, Japan.
Exp Eye Res. 2013 Nov;116:308-11. doi: 10.1016/j.exer.2013.10.001. Epub 2013 Oct 12.
The vascular endothelium responds to shear stress generated by blood flow and changes functions to regulate blood flow and maintain tissue homeostasis. Recently, we found that arteriolar high shear stress leads to increased expression of vasodilatory and antithrombotic genes in human retinal microvascular endothelial cells (HRMECs). However, it is unknown whether low shear stress, which is induced by hypoperfusion particularly in the retinal venules where leukocyte-endothelial interactions mainly occur, affects the retinal endothelial function. We studied the effect of low shear stress on proinflammatory gene expression in HRMECs. The cells were cultured on glass plates and exposed to laminar shear stresses of 0 (static), 1.5 (relatively low flow), and 15 dyne/cm(2) (relatively high flow) for 24 h using parallel plate-type flow-loading devices. The mRNA expressions of adhesion molecules, cytokines and chemokines, and procoagulant factors were evaluated using real-time reverse-transcription polymerase chain reaction. HRMECs exposed to 1.5 dyne/cm(2) significantly up-regulated the mRNA expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. The cells exposed to 1.5 dyne/cm(2) of stress also had increased cytokine/chemokine mRNA expression, i.e., interleukin (IL)-6, IL-8, platelet-derived growth factor-B, and monocyte chemotactic protein-1. Procoagulant factors, i.e., tissue factor and plasminogen activator inhibitor-1 mRNA, increased significantly with exposure to 1.5 dyne/cm(2) of stress. Our results showed that relatively low shear stress causes up-regulation of proinflammatory genes in HRMECs, suggesting that decreased shear stress due to vascular hypoperfusion might change the phenotypic characterization of the retinal vascular endothelium and be associated with leukocyte-endothelial interactions.
血管内皮细胞对血流产生的切应力做出反应，并改变功能以调节血流和维持组织内稳态。最近，我们发现，小动脉的高切应力导致人视网膜微血管内皮细胞（HRMECs）中血管舒张和抗血栓形成基因的表达增加。然而，尚不清楚低切应力（特别是在白细胞-内皮细胞相互作用主要发生的视网膜小静脉中，由于灌注不足而引起）是否会影响视网膜内皮功能。我们研究了低切应力对 HRMECs 中促炎基因表达的影响。使用平行板式流加载装置，将细胞培养在玻璃平板上，并使其分别暴露于 0（静态）、1.5（相对低流量）和 15 达因/平方厘米（相对高流量）的层流切应力下 24 小时。使用实时逆转录聚合酶链反应评估粘附分子、细胞因子和趋化因子以及促凝血因子的 mRNA 表达。暴露于 1.5 达因/平方厘米的 HRMECs 显著上调了细胞间粘附分子-1、血管细胞粘附分子-1 和 E-选择素的 mRNA 表达。暴露于 1.5 达因/平方厘米的细胞也具有增加的细胞因子/趋化因子 mRNA 表达，即白细胞介素（IL）-6、IL-8、血小板衍生生长因子-B 和单核细胞趋化蛋白-1。组织因子和纤溶酶原激活物抑制剂-1 的 mRNA 表达也随着暴露于 1.5 达因/平方厘米的切应力显著增加。我们的结果表明，相对低切应力导致 HRMECs 中促炎基因的上调，提示由于血管灌注不足导致的切应力降低可能改变视网膜血管内皮的表型特征，并与白细胞-内皮细胞相互作用有关。
