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Cardiovasc Res. 2008 Oct 1;80(1):131-7. doi: 10.1093/cvr/cvn169. Epub 2008 Jun 19.

The immunoadhesin glycoprotein VI-Fc regulates arterial remodelling after mechanical injury in ApoE-/- mice.

Author information

1
DVM, Medizinische Klinik III, Abt. Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Otfried-Müller-Str.10, 72076 Tübingen, Germany. tanja.schoenberger@med.uni-tuebingen.de

Abstract

AIMS:

Rupture of advanced atherosclerotic plaques initiates platelet activation and aggregation as subendothelial collagen is exposed. Platelet collagen receptor glycoprotein VI (GPVI) was found to bind preferentially to the core region of human plaques. Consequently, platelets contribute to inflammatory processes and trigger atherosclerotic lesion progression. In this study, we examined binding of soluble platelet collagen receptor GPVI-Fc to atherosclerotic lesions and its effect on platelet-triggered athero-progression and neointima formation after wire-induced carotid injury.

METHODS AND RESULTS:

For binding studies after ligation-induced arterial injury, the left common carotid artery of C57BL/6J mice was ligated. For binding studies at spontaneously formed atherosclerotic lesion sites, Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a 0.25% cholesterol diet over 16 weeks. Binding of [(124)I]GPVI-Fc was monitored by autoradiography 48 h after intravenous injection and by immunostaining. To study the effect of GPVI-Fc on neointima formation vs. control-Fc, a wire-induced injury of the left A. carotis communis of ApoE(-/-)-mice was performed. Mice were treated intraperitoneally with GPVI-Fc for 8 days and neointima formation was assessed 4 weeks after intervention. [(124)I]GPVI-Fc preferentially bound to injury sites after carotid ligation in C57BL/6J mice and to lipid-rich atherosclerotic lesions of the carotid artery and aortic arch in uninjured ApoE(-/-)-mice. Histological examinations of wire-injured carotid arteries showed that neointima formation was significantly reduced in GPVI-Fc-treated ApoE(-/-) mice compared to ApoE(-/-) mice receiving control-Fc (P < 0.05).

CONCLUSION:

GPVI-Fc preferentially bound to sites of vascular injury and was able to inhibit neointima formation after wire-induced vascular injury in ApoE(-/-) mice. Thus, soluble GPVI-Fc might be also a promising compound to attenuate lesion progression after plaque rupture.

PMID:
18566102
DOI:
10.1093/cvr/cvn169
[Indexed for MEDLINE]
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