Platelets activated by collagen through immunoreceptor tyrosine-based activation motif play pivotal role in initiation and generation of neointimal hyperplasia after vascular injury

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 gamma chain (FcRgamma) playing a pivotal role. Methods and Results-We examined the role of colla-en-stimulated platelets in the development of injury-induced neointimal formation by using mice deficient in FcRgamma. The left femoral arteries of 8- to 12-week-old FcR-gamma-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-gamma-knockout mice compared with wild-type mice. At 7 days after injury, staining with anti-neutrophil antibody showed fewer neutrophils in FcRgamma-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 FcRgamma-knockout mice than in wild-type mice (for neointimal area, 16 635+/-1406 versus 31 483+/-2309 mum(2), 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 FcRgamma may play important roles in the initiation and generation of neointimal hyperplasia after balloon injury through the activation of platelets by collagen.