Inoue Teruo, Uchida Toshihiko, Sakuma Masashi, Imoto Yoshitaka, Ozeki Yasushi, Ozaki Yukio, Hikichi Yutaka, Node Koichi
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan.
J Am Coll Cardiol. 2004 Oct 6;44(7):1408-14. doi: 10.1016/j.jacc.2004.06.066.
The aim of this study was to confirm clinically a hypothesis that cilostazol inhibits leukocyte Mac-1, leading to prevention of post-stent restenosis.
The platelet phosphodiesterase III inhibitor called cilostazol also inhibits alpha-granule release of P-selectin in platelets. The P-selectin-mediated platelet-leukocyte interaction promotes activation and upregulation of leukocyte Mac-1 after coronary stenting, which plays a key role on the mechanism of restenosis. Thus, cilostazol's potential inhibition of this process may lead to prevention of restenosis.
Using flow cytometric analysis of whole blood obtained from the coronary sinus, the expression of platelet membrane glycoproteins and neutrophil adhesion molecules was observed in 70 consecutive patients undergoing coronary stenting. The patients were randomly assigned to either a cilostazol or ticlopidine group before stent placement.
The restenosis rate was lower (15% vs. 31%, p < 0.05) in the cilostazol group (n = 34) than in the ticlopidine group (n = 32). A stent-induced increase in platelet P-selectin (CD62P) expression and an increase in neutrophil Mac-1 (CD11b) expression were suppressed in the cilostazol group compared with the ticlopidine group. Angiographic late lumen loss was correlated with the relative changes in platelet P-selectin and neutrophil Mac-1 at 48 h after coronary stenting.
Cilostazol may have effects on suppression of P-selectin-mediated platelet activation, platelet-leukocyte interaction, and subsequent Mac-1-mediated leukocyte activation, which might lead to a reduced restenosis rate after coronary stent implantation.
本研究旨在通过临床验证西洛他唑抑制白细胞Mac-1从而预防支架置入术后再狭窄这一假说。
血小板磷酸二酯酶III抑制剂西洛他唑还可抑制血小板中P-选择素的α-颗粒释放。P-选择素介导的血小板-白细胞相互作用会促进冠状动脉支架置入术后白细胞Mac-1的激活和上调，而这在再狭窄机制中起关键作用。因此，西洛他唑对这一过程的潜在抑制作用可能会预防再狭窄。
通过对从冠状窦采集的全血进行流式细胞术分析，观察了70例连续接受冠状动脉支架置入术患者的血小板膜糖蛋白和中性粒细胞黏附分子的表达情况。在支架置入前，将患者随机分为西洛他唑组或噻氯匹定组。
西洛他唑组（n = 34）的再狭窄率低于噻氯匹定组（n = 32）（15%对31%，p < 0.05）。与噻氯匹定组相比，西洛他唑组中支架诱导的血小板P-选择素（CD62P）表达增加以及中性粒细胞Mac-1（CD11b）表达增加受到抑制。冠状动脉支架置入术后48小时，血管造影晚期管腔丢失与血小板P-选择素和中性粒细胞Mac-1的相对变化相关。
西洛他唑可能对抑制P-选择素介导的血小板激活、血小板-白细胞相互作用以及随后的Mac-1介导的白细胞激活有作用，这可能导致冠状动脉支架植入术后再狭窄率降低。
