Evaluation of Matrix Metalloproteinases in Atherosclerosis Using a Novel Noninvasive Imaging Approach
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- Eric Lancelot
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Vardan Amirbekian
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Irène Brigger
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Jean-Sébastien Raynaud
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Sébastien Ballet
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Christelle David
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Olivier Rousseaux
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Soizic Le Greneur
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Marc Port
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Henri R. Lijnen
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Patrick Bruneval
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Jean-Baptiste Michel
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Tanja Ouimet
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Bernard Roques
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Smbat Amirbekian
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Fabien Hyafil
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Esad Vucic
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Juan Gilberto S. Aguinaldo
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Claire Corot
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
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- Zahi A. Fayad
- From the Imaging Science Laboratories, Department of Radiology, the Zena and Michael A. Wiener Cardiovascular Institute, the Marie-Josée and Henry R. Kravis Cardiovascular Health Center, and Department of Medicine, Mount Sinai School of Medicine (V.A., S.A., F.H., E.V., J.G.S.A., Z.A.F); Guerbet (E.L., I.B., J-S.R., S.B., C.D., O.R., S.LG., M.P., C.C.), Aulnay-sous-Bois, France; Center for Molecular and Vascular Biology (H.R.L.), University of Leuven, Belgium; INSERM U-652 (P.B.), Paris, France;...
抄録
<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> Despite great advances in our knowledge, atherosclerosis continues to kill more people than any other disease in the Western world. This is because our means of identifying truly vulnerable patients is limited. Prediction of atherosclerotic plaque rupture may be addressed by MRI of activated matrix metalloproteinases (MMPs), a family of enzymes that have been implicated in the vulnerability of plaques prone to rupture. This study evaluated the ability of the novel gadolinium-based MRI contrast agent P947 to target MMPs in atherosclerotic plaques. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> The affinity of P947 toward activated MMPs was demonstrated in vitro. The affinity and specificity of P947 toward matrix metalloproteinase (MMP)-rich plaques was evaluated both in vivo using ApoE <jats:sup>−/−</jats:sup> mice and ex vivo in hyperlipidemic rabbits. Gadolinium content quantification and MRI showed a preferential accumulation of P947 in atherosclerotic lesions compared with the nontargeted reference compound, Gd-DOTA. The ex vivo assay on rabbit plaques revealed a higher uptake of P947. Moreover, using human carotid artery endarterectomy specimens, P947 facilitated discrimination between histologically defined MMP-rich and MMP-poor plaques. An in vivo MRI investigation in mice revealed that P947 greatly improved the ability to visualize and delineate atherosclerotic plaques. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> P947 may be a useful tool for the detection and characterization of the MMP-rich atherosclerotic plaques. </jats:p>
収録刊行物
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- Arteriosclerosis, Thrombosis, and Vascular Biology
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Arteriosclerosis, Thrombosis, and Vascular Biology 28 (3), 425-432, 2008-03
Ovid Technologies (Wolters Kluwer Health)