Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in restenosis after coronary stent implantation.
OBJECTIVE
The aim of this study was to confirm clinically a hypothesis that cilostazol inhibits leukocyte Mac-1, leading to prevention of post-stent restenosis.


BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Inoue
Teruo
T
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan. inouete@med.saga-uc.ac.jp <inouete@med.saga-uc.ac.jp>
Uchida
Toshihiko
T
Sakuma
Masashi
M
Imoto
Yoshitaka
Y
Ozeki
Yasushi
Y
Ozaki
Yukio
Y
Hikichi
Yutaka
Y
Node
Koichi
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000368:Aged; D000077407:Cilostazol; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D023903:Coronary Restenosis / Q000097:blood / Q000517:prevention & control*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D019007:P-Selectin / Q000097:blood / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012107:Research Design; D015607:Stents / Q000009:adverse effects; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013988:Ticlopidine / Q000494:pharmacology / Q000627:therapeutic use*
D016177:Macrophage-1 Antigen; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol; D013988:Ticlopidine