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

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-06, Vol.105 (24), p.2893-2898
• Main Authors: ARITA, Yukio, KIHARA, Shinji, NAKAMURA, Tadashi, SHIMOMURA, Lichiro, MURAGUCHI, Masahiro, OHMOTO, Yasukazu, FUNAHASHI, Tohru, MATSUZAWA, Yuji, OUCHI, Noriyuki, MAEDA, Kazuhisa, KURIYAMA, Hiroshi, OKAMOTO, Yoshihisa, KUMADA, Masahiro, HOTTA, Kikuko, NISHIDA, Makoto, TAKAHASHI, Masahiko
• Format: Article
• Language: English
• Subjects: Adipocytes - chemistry; Adiponectin; Aorta - cytology; Becaplermin; Biological and medical sciences; Blood Proteins - metabolism; Blood Proteins - pharmacology; Blood vessels and receptors; Cell Division; Cell Movement; Cells, Cultured; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Growth Inhibitors - metabolism; Growth Inhibitors - pharmacology; Growth Substances - pharmacology; Humans; Intercellular Signaling Peptides and Proteins; Mitogen-Activated Protein Kinases - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Phosphorylation; Platelet-Derived Growth Factor - antagonists & inhibitors; Platelet-Derived Growth Factor - metabolism; Proteins - metabolism; Proteins - pharmacology; Proto-Oncogene Proteins c-sis; Receptors, Growth Factor - antagonists & inhibitors; Receptors, Growth Factor - metabolism; Signal Transduction - drug effects; Vertebrates: cardiovascular system
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000018622.84402.ff

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. 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.