ICAM-1 and p38 MAPK mediate fibrinogen-induced migration of human vascular smooth muscle cells.
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.
Rauch
Bernhard H
BH
Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum, Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Müschenborn
Birgit
B
Braun
Marina
M
Weber
Artur-Aron
AA
Schrör
Karsten
K
D000077284:Abciximab; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005340:Fibrinogen / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000077284:Abciximab; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D002867:Chromones; D004247:DNA; D004791:Enzyme Inhibitors; D005340:Fibrinogen; D005419:Flavonoids; D007093:Imidazoles; D007140:Immunoglobulin Fab Fragments; D018799:Intercellular Adhesion Molecule-1; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D051057:Proto-Oncogene Proteins c-akt; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one