ICAM-1 and p38 MAPK mediate fibrinogen-induced migration of human vascular smooth muscle cells

Eur J Pharmacol. 2007 Dec 22;577(1-3):54-7. doi: 10.1016/j.ejphar.2007.08.041. Epub 2007 Sep 11.

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

  • Abciximab
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Cell Movement / drug effects
  • Chemotaxis / drug effects
  • Chromones / pharmacology
  • DNA / biosynthesis
  • DNA / genetics
  • Enzyme Inhibitors / pharmacology
  • Fibrinogen / pharmacology*
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Humans
  • Imidazoles / pharmacology
  • Immunoblotting
  • Immunoglobulin Fab Fragments / pharmacology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Adhesion Molecule-1 / physiology*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Morpholines / pharmacology
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / drug effects*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyridines / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / physiology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Immunoglobulin Fab Fragments
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Pyridines
  • Intercellular Adhesion Molecule-1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Fibrinogen
  • DNA
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Abciximab