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(Circulation. 2003;107:1757.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Stent-Induced Expression and Activation of the Leukocyte Integrin Mac-1 Is Associated With Neointimal Thickening and Restenosis

Teruo Inoue, MD; Toshihiko Uchida, MD; Isao Yaguchi, MD; Yoshihiko Sakai, MD; Kan Takayanagi, MD; Shigenori Morooka, MD

From the Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Saitama, Japan.

Correspondence to Teruo Inoue, MD, Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minamikoshigaya, Koshigaya City, Saitama 343-8555, Japan. E-mail inouet{at}dokkyomed.ac.jp

Background— Increased expression of the ß₂ integrin Mac-1 (CD11b/CD18, _Mß₂), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions.

Methods and Results— Expression of CD11b (-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R=0.42, P<0.01) and the 8B2 increase (R=0.55, P<0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss.

Conclusion— Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis.

Key Words: stents • restenosis • hyperplasia • leukocytes • cell adhesion molecules

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