Abstract
Fibrinogen deposition in the vessel wall represents an independent atherogenic risk factor. In Boyden-chamber assays, fibrinogen concentration-dependently (1-100 microM) induced migration of human vascular smooth muscle cells (SMC). This was inhibited by antibodies to intercellular adhesion molecule-1 (ICAM-1, 10 microg/ml), and by inhibitors of PI3-kinase (LY294002, 10 microM) and MAPK (mitogen-activated protein kinase) p38 (SB203580, 10 microM). The MEK (MAP kinase kinase) inhibitor PD98059 (10 muM) and the GPIIb/IIIa antagonist abciximab (10 mug/ml) had no effect. ICAM-1 antibodies inhibited fibrinogen-induced Akt and p38 phosphorylation. Thus fibrinogen stimulates human SMC migration through binding to ICAM-1 and activation of Akt and p38.
MeSH terms
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Abciximab
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Cell Movement / drug effects
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Chemotaxis / drug effects
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Chromones / pharmacology
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DNA / biosynthesis
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DNA / genetics
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Enzyme Inhibitors / pharmacology
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Fibrinogen / pharmacology*
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Flavonoids / pharmacology
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Flow Cytometry
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Humans
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Imidazoles / pharmacology
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Immunoblotting
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Immunoglobulin Fab Fragments / pharmacology
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Intercellular Adhesion Molecule-1 / metabolism
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Intercellular Adhesion Molecule-1 / physiology*
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Morpholines / pharmacology
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Muscle, Smooth, Vascular / cytology*
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Myocytes, Smooth Muscle / drug effects*
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
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Pyridines / pharmacology
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / physiology*
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Immunoglobulin Fab Fragments
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Platelet Glycoprotein GPIIb-IIIa Complex
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Pyridines
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Intercellular Adhesion Molecule-1
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Fibrinogen
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DNA
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Proto-Oncogene Proteins c-akt
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p38 Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Abciximab