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Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in restenosis after coronary stent implantation

Teruo Inoue, MD, FACC^*,,*, Toshihiko Uchida, MD, Masashi Sakuma, MD, Yoshitaka Imoto, Yasushi Ozeki, PhD, Yukio Ozaki, MD, Yutaka Hikichi, MD^* and Koichi Node, MD^*

^* Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan
Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Japan
Yufu Itonaga Company, Tokyo, Japan
Department of Laboratory Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho, Japan

View larger version (12K): [in a new window]   Figure 1 Serial changes in P-selectin (CD62P) on the surface of platelets (left panel) and Mac-1 (CD11b) on the surface of neutrophils (right panel) after coronary stenting. Platelet P-selectin and neutrophil Mac-1 increased after coronary stenting in a time-dependent manner, and the maximum increase was at 48 h. Both changes were suppressed in the cilostazol group compared with the ticlopidine group. *p < 0.05 vs. baseline. **p < 0.01 vs. baseline. ***p < 0.001 vs. baseline. p < 0.05 for intergroup comparison. p < 0.01 for intergroup comparison. Open circles = cilostazol group (n = 34); solid circles = ticlopidine group (n = 32). MFI = mean channel fluorescence intensity.

View larger version (21K): [in a new window]   Figure 2 Correlation between angiographic late lumen loss and relative changes in platelet P-selectin (left panel) and neutrophil CD11b (right panel) at 48 h after coronary stenting. Open circles = cilostazol group (n = 34); solid circles = ticlopidine group (n = 32).

View larger version (36K): [in a new window]   Figure 3 Cilostazol's direct action for Mac-1 (CD11b). Cilostazol inhibited an expression of Mac-1 on surface of neutrophils in vitro in a dose-dependent manner, compared with the control (+dimethyl sulfoxide [DMSO] +formyl-methyonyl leucyl phenylalanine [FMLP]). *p < 0.05. **p < 0.01.