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

Article

关键词: ADIPOSE-SPECIFIC PROTEIN;    INSULIN-RESISTANCE;    VISCERAL FAT;    EXPRESSION;    OBESITY;    GENE;    ACCUMULATION;    MACROPHAGES;    RECEPTORS;    COLLAGENS;   

DOI  :  10.1161/01.CIR.0000018622.84402.FF

来源: SCIE

【 摘 要 】

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 [H-3] 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 I-125-PDGF-BB and significantly inhibited the association of I-125-PDGF-BB with HASMCs, but no effects were observed on the binding of I-125-PDGF-AA or I-125-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 a-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.

【 授权许可】

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