Department of Neurosurgery, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
J Vasc Surg. 2012 Feb;55(2):506-16. doi: 10.1016/j.jvs.2011.07.087.
An inflammatory reaction in vascular tissue is a potential factor linking restenosis after angioplasty. Although cilostazol, a selective phosphodiesterase type 3 inhibitor that is a unique antiplatelet drug and vasodilator, has been reported to be anti-inflammatory, its effect on the inflammatory action of mononuclear cells homing to endothelial cells is not clearly understood. In this study, whether cilostazol inhibits neointimal formation and improves inflammatory actions by inhibiting sialyl Lewis X (SLX) expression on mononuclear cells and E-selectin expression on endothelial cells was evaluated.
The effect of cilostazol (1, 3, 10, 30 μM) on expression of E-selectin in human umbilical vein endothelial cells and SLX in rat mononuclear cells stimulated with lipopolysaccharide by immunofluorescence and real-time polymerase chain reaction (n = 3) was studied. Additionally, a double-balloon injury model was used on rat carotid arteries to evaluate vascular intimal hyperplasia. 0.1% cilostazol was administered 3 days before the first balloon injury, and the second balloon injury was performed 7 days after the first injury. Cilostazol administration was continued until rats were sacrificed 14 days after the second angioplasty. The expression of SLX on mononuclear cells and E-selectin on endothelial cells by immunofluorescence (n = 10) and real-time polymerase chain reaction (n = 5) were studied.
Cilostazol effectively inhibited the expression of SLX on mononuclear cells and E-selectin on endothelial cells. Cilostazol inhibited the migration of mononuclear cells in neointimal regions and neointimal hyperplasia after balloon injury. The numbers of macrophages and T-lymphocytes and the hyperplasia area in neointimal regions decreased from 71.06 ± 20.04, 1121 ± 244.4 cells per section, 206,400 ± 96,150 mm(2) to 29.65 ± 16.73, 374.2 ± 124.5 cells per section, and 101,900 ± 16,150 mm(2) due to the administration of cilostazol.
These results demonstrate that the protective effect of cilostazol against neointimal hyperplasia may be mediated by its anti-inflammatory actions of mononuclear cells homing to endothelial cells by decreasing SLX and E-selectin expression.
It is reported that cilostazol inhibits neointimal hyperplasia by decreasing the expression of some cell-adhesion molecules. We evaluated the effects of cilostazol for the expression of sialyl Lewis X (SLX) on mononuclear cells and E-selectin on endothelial cells, which interaction is the first step of inflammation action. Cilostazol was thought to show the anti-inflammatory actions by decreasing SLX and E-selectin expression in addition to decreasing the expression of some cell-adhesion molecules.
血管组织中的炎症反应是经皮腔内血管成形术后再狭窄的潜在关联因素。西洛他唑是一种选择性磷酸二酯酶 3 抑制剂，是一种独特的抗血小板药物和血管扩张剂，已被报道具有抗炎作用，但它对单核细胞归巢到内皮细胞的炎症作用的影响尚不清楚。在这项研究中，评估了西洛他唑通过抑制单核细胞上的唾液酸化路易斯 X（SLX）表达和内皮细胞上的 E-选择素表达，是否抑制新生内膜形成并改善炎症作用。
通过免疫荧光和实时聚合酶链反应（n = 3）研究了西洛他唑（1、3、10、30 μM）对脂多糖刺激的人脐静脉内皮细胞中 E-选择素和大鼠单核细胞中 SLX 表达的影响。此外，还在大鼠颈动脉上使用双球囊损伤模型来评估血管内膜增生。在第一次球囊损伤前 3 天给予 0.1%西洛他唑，第一次损伤后 7 天进行第二次球囊损伤。在第二次血管成形术后 14 天处死大鼠前，继续给予西洛他唑。通过免疫荧光（n = 10）和实时聚合酶链反应（n = 5）研究了单核细胞上的 SLX 表达和内皮细胞上的 E-选择素表达。
西洛他唑能有效抑制单核细胞上的 SLX 表达和内皮细胞上的 E-选择素表达。西洛他唑抑制了单核细胞在新生内膜区的迁移和球囊损伤后的内膜增生。由于西洛他唑的给药，新生内膜区的巨噬细胞和 T 淋巴细胞数量和增生面积从 71.06 ± 20.04、1121 ± 244.4 个/切片、206400 ± 96150 mm(2)减少到 29.65 ± 16.73、374.2 ± 124.5 个/切片和 101900 ± 16150 mm(2)。
这些结果表明，西洛他唑通过降低 SLX 和 E-选择素的表达来抑制单核细胞归巢到内皮细胞的炎症作用，从而对新生内膜增生具有保护作用。
据报道，西洛他唑通过降低某些细胞黏附分子的表达来抑制新生内膜增生。我们评估了西洛他唑对单核细胞上的唾液酸化路易斯 X（SLX）和内皮细胞上的 E-选择素表达的影响，这是炎症作用的第一步。除了降低某些细胞黏附分子的表达外，西洛他唑可能还通过降低 SLX 和 E-选择素的表达来发挥抗炎作用。
