doi: 10.1161/hc0802.105256
(Circulation. 2002;105:912.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Platelets Activated by Collagen Through Immunoreceptor Tyrosine-Based Activation Motif Play Pivotal Role in Initiation and Generation of Neointimal Hyperplasia After Vascular Injury
From the Department of Cardiology (H.K., Y. Katoh, N.T., Y. Kashiwakura, S.I., H.D.) and the Allergy Research Center (H.K., N.T.), Juntendo University School of Medicine, Tokyo, and the Department of Molecular Cell Immunology and Allergology (C.R.), Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan.
Correspondence to Youichi Katoh, MD, PhD, Department of Cardiology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail katoyo{at}med.juntendo.ac.jp
Background— Platelet adhesion on components of the extracellular matrix and platelet activation by those components are crucial for the arrest of posttraumatic bleeding, but they can also harm tissue by occluding diseased vessels. Recent studies have shown that the activation of platelets by collagen is mediated through the same pathway used by immune receptors, with an immunoreceptor tyrosine-based activation motif on the Fc receptor 
chain (FcR) playing a pivotal role.
Methods and Results— We examined the role of collagen-stimulated platelets in the development of injury-induced neointimal formation by using mice deficient in FcR. The left femoral arteries of 8- to 12-week-old FcR-deficient mice (n=16) and C57BL/6 (wild-type) mice (n=16) were injured by a straight spring wire (0.35-mm diameter). Segments of the injured and uninjured femoral arteries were excised at 7 days and 28 days after the vascular injury. Arterial segments were examined by immunohistochemistry and electron microscopy. Two hours after injury, electron microscopy showed marked decreases in platelet adhesion and neutrophil attachment to the vascular wall surface in FcR-knockout mice compared with wild-type mice. At 7 days after injury, staining with anti-neutrophil antibody showed fewer neutrophils in FcR-knockout mice than in wild-type mice. Computer-aided morphometry performed to measure the neointimal area, intima/media ratio, and stenotic area at 28 days after injury showed a significantly smaller ratio and area in FcR-knockout mice than in wild-type mice (for neointimal area, 16 635±1406 versus 31 483±2309 µm2, respectively; for intima/media ratio, 1.25±0.40 versus 2.68±0.04, respectively; and for stenotic area, 26.8±2.1% versus 49.3±4.1%, respectively).
Conclusions— These results demonstrate that FcR may play important roles in the initiation and generation of neointimal hyperplasia after balloon injury through the activation of platelets by collagen.
Key Words: platelets • restenosis • immune system • collagen
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