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Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.

BACKGROUND: Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods and Results- HASMC proliferation was estimated by [(3)H] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to (125)I-PDGF-BB and significantly inhibited the association of (125)I-PDGF-BB with HASMCs, but no effects were observed on the binding of (125)I-PDGF-AA or (125)I-heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular signal-related kinase (ERK) phosphorylation and PDGF beta-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA-stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF alpha-receptor or EGF receptor. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.

Pubmed ID: 12070119


  • Arita Y
  • Kihara S
  • Ouchi N
  • Maeda K
  • Kuriyama H
  • Okamoto Y
  • Kumada M
  • Hotta K
  • Nishida M
  • Takahashi M
  • Nakamura T
  • Shimomura I
  • Muraguchi M
  • Ohmoto Y
  • Funahashi T
  • Matsuzawa Y



Publication Data

June 18, 2002

Associated Grants


Mesh Terms

  • Adipocytes
  • Adiponectin
  • Aorta
  • Blood Proteins
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Growth Inhibitors
  • Growth Substances
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mitogen-Activated Protein Kinases
  • Muscle, Smooth, Vascular
  • Phosphorylation
  • Platelet-Derived Growth Factor
  • Proteins
  • Proto-Oncogene Proteins c-sis
  • Receptors, Growth Factor
  • Signal Transduction