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Mouse Carotid Artery Ligation Induces Platelet-Leukocyte–Dependent Luminal Fibrin, Required for Neointima Development by Tomihisa Kawasaki, Mieke Dewerchin,

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Presentation on theme: "Mouse Carotid Artery Ligation Induces Platelet-Leukocyte–Dependent Luminal Fibrin, Required for Neointima Development by Tomihisa Kawasaki, Mieke Dewerchin,"— Presentation transcript:

1 Mouse Carotid Artery Ligation Induces Platelet-Leukocyte–Dependent Luminal Fibrin, Required for Neointima Development by Tomihisa Kawasaki, Mieke Dewerchin, H. Roger Lijnen, I. Vreys, Jos Vermylen, and Marc F. Hoylaerts Circulation Research Volume 88(2): February 2, 2001 Copyright © American Heart Association, Inc. All rights reserved.

2 Platelet deposition after carotid artery ligation.
Platelet deposition after carotid artery ligation. Immunohistochemical detection of platelets in murine blood buffy coat (a), murine spleen (b), and an experimental injury-induced platelet-rich thrombus, produced as in Reference 29 (c). Shown are platelet microaggregates, indicated by white arrows, at the endothelial lumen of the carotid artery in wt mice 1 day after ligation (d); decoration of adhering leukocytes with platelets 1 day (d) and 3 days (e) after ligation (yellow arrows); and extensive platelet thrombus 1 week after ligation (f). Bar=50 μm. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

3 Carotid artery morphology after ligation.
Carotid artery morphology after ligation. H&E staining of cross sections of the ligated carotid artery of C57BL/6J mice after 1 day (a), 3 days (b), 1 week (c), and 2 weeks (d) and of busulfan-treated C57BL/6J mice (e) and of FVIII−/− mice at day 3 (f). Bar=100 μm. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

4 Coagulation in ligated carotid artery.
Coagulation in ligated carotid artery. Fibrin staining (brown) in wt mice (a through c) and u-PA−/− mice (d through f). Carotid artery cross sections 3 days (a), 1 week (b and d through f), and 2 weeks (c) after ligation. Smooth muscle cells migrating over the fibrin matrix are indicated with arrows Bar=100 μm. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

5 Tissue factor expression after ligation.
Tissue factor expression after ligation. Expression of tissue factor (brown) in early luminal deposits and luminal cells 3 days after carotid artery ligation in wt mice (a) and in areas adjacent to the neointima after 1 week (b) or 2 weeks (c). d, presence of tissue factor in the neointima after 2 weeks. Bar=50 μm. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

6 Neointima formation in the ligated murine carotid artery.
Neointima formation in the ligated murine carotid artery. Cross-sectional area within the EEL and IEL as a function of time after ligation of the carotid artery in C57BL/6J control mice. The free-luminal surface and derived-media index and luminal stenosis data are mean±SEM for the number of animals indicated in parentheses. *P<0.05; **P<0.01. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

7 Carotid artery neointima formation in gene-deficient mice.
Carotid artery neointima formation in gene-deficient mice. Degree of neointima formation 1 and 2 weeks after carotid artery ligation in FVIII−/−, u-PA−/−, t-PA−/−, PAI-1−/−, and α2-AP−/− mice (light bars) in comparison with wt controls with identical genetic background (black bars); data are mean±SEM for the number of animals indicated in parentheses. *P<0.05; **P<0.01. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

8 Thrombocytopenia and intimal proliferation.
Thrombocytopenia and intimal proliferation. Degree of neointima formation 1 and 2 weeks after carotid artery ligation in C57BL/6J mice after partial thrombocytopenia induction compared with vehicle-treated controls. **P<0.01. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.

9 Fibrinogen depletion and intimal proliferation.
Fibrinogen depletion and intimal proliferation. Degree of stenosis 2 weeks after carotid artery ligation in C57BL/6J mice partially depleted in plasma fibrinogen by injection with ancrod 8 hours before and 2 days after ligation (early depletion) or by ancrod injection on days 6, 8, 10, and 12 (late depletion) compared with vehicle-treated controls. **P<0.01. Tomihisa Kawasaki et al. Circ Res. 2001;88: Copyright © American Heart Association, Inc. All rights reserved.


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