Adams M R, Jessup W, Hailstones D, Celermajer D S
Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
Circulation. 1997 Feb 4;95(3):662-8. doi: 10.1161/01.cir.95.3.662.
Monocyte adhesion to endothelial cells is a key early event in atherogenesis. Because L-arginine has been shown to reduce atheroma and to decrease monocyte-endothelial cell adhesion in an animal model of atherosclerosis, we studied the effects of L-arginine on human monocyte adhesion to human endothelial cells and endothelial expression of cell adhesion molecules.
Human umbilical vein endothelial cells (HUVECs) were grown to confluence, then incubated for 24 hours with arginine-deficient media to which was added saline (control), 100 or 1000 mumol/L L-arginine, 100 mumol/L D-arginine, 100 mumol/L NG-monomethyl-L-arginine (L-NMMA), or 100 mumol/L L-arginine with 100 mumol/L L-NMMA. Human monocytes obtained by elutriation were incubated for 1 hour with HUVECs, and adhesion was measured by light microscopy. Compared with control, monocyte adhesion was reduced by L-arginine (59 +/- 10%, P = .01) and increased by L-NMMA (123 +/- 20%, P = .01). Surface expression of cell adhesion molecules by HUVECs was assessed by an ELISA under the above conditions with and without stimulation with interleukin-1 beta. Expression of ICAM-1 was reduced with both concentrations of L-arginine compared with control in both the basal (43 +/- 12%, P < .01), and stimulated (46 +/- 15%, P < .01) states, which correlated with decreased levels of mRNA. Expression of VCAM-1 was reduced only in the stimulated state and only in the presence of 1000 mumol/L L-arginine (72 +/- 24%, P = .02).
L-Arginine reduces human monocyte adhesion to endothelial cells and decreases expression of certain endothelial cell adhesion molecules.
单核细胞与内皮细胞的黏附是动脉粥样硬化形成早期的关键事件。由于在动脉粥样硬化动物模型中，L-精氨酸已被证明可减少动脉粥样硬化斑块并降低单核细胞与内皮细胞的黏附，因此我们研究了L-精氨酸对人单核细胞与人内皮细胞黏附以及内皮细胞黏附分子表达的影响。
将人脐静脉内皮细胞（HUVECs）培养至汇合，然后用添加了生理盐水（对照）、100或1000 μmol/L L-精氨酸、100 μmol/L D-精氨酸、100 μmol/L NG-单甲基-L-精氨酸（L-NMMA）或100 μmol/L L-精氨酸与100 μmol/L L-NMMA的精氨酸缺乏培养基孵育24小时。通过淘洗获得的人单核细胞与HUVECs孵育1小时，通过光学显微镜测量黏附情况。与对照相比，L-精氨酸可降低单核细胞黏附（59±10%，P = 0.01），而L-NMMA可增加单核细胞黏附（123±20%，P = 0.01）。在上述条件下，无论有无白细胞介素-1β刺激，均通过酶联免疫吸附测定（ELISA）评估HUVECs表面黏附分子的表达。与对照相比，在基础状态（43±12%，P < 0.01）和刺激状态（46±15%，P < 0.01）下，两种浓度的L-精氨酸均使细胞间黏附分子-1（ICAM-1）的表达降低，这与mRNA水平降低相关。血管细胞黏附分子-1（VCAM-1）的表达仅在刺激状态下且仅在存在1000 μmol/L L-精氨酸时降低（72±24%，P = 0.02）。
L-精氨酸可降低人单核细胞与内皮细胞的黏附，并减少某些内皮细胞黏附分子的表达。
