Vaspin has insulin-sensitizing effects, as well as additional beneficial effects on metabolic diseases. However, little is known about the direct effects of vaspin on vascular complications mediated by diabetes. The objective of this study is to determine the efficacy and mechanism of vaspin on hyperglycemia-induced vascular smooth muscle cells (VSMCs) proliferation, chemokinesis and cell signaling.
Rat VSMCs proliferation was determined with 5-ethynyl-2′-deoxyuridine cell proliferation assays, chemokinesis was monitored with scratch assays, and reactive oxygen species (ROS) production was assessed using H2DCFDA and SOD-inhibited reduction of ferricytochrome c assay. Luciferase activity is assayed using a Dual Luciferase Reporter Assay System. Cell signaling is assessed by immunblotting.
Vaspin significantly inhibited VSMCs proliferation and chemokinesis, as well as ROS generation and NADPH oxidase activity, induced by high glucose (HG) treatment. Compared with HG, vaspin significantly decreased VSMCs proliferation by 40 ± 8% at 100 ng/ml. Vaspin also decreased ROS production by 16 ± 8% at 100 ng/ml and 30 ± 8% at 300 ng/ml (all P < 0.01). Vaspin significantly abolished HG-induced phosphorylation of oxidase subunits p47phox, Akt, p38, and JNK1/2 without affecting their total levels, and attenuated HG-induced phosphorylation of insulin receptor and its downstream IRS-1 and IRS-2. For downstream targets, NF-κB activity and IκBα phosphorylation were both enhanced significantly after HG stimulation, and these effects were inhibited by vaspin. Vaspin also significantly abolished HG-induced PCNA and cyclin D1 expression.
Vaspin inhibits HG-induced VSMCs proliferation and chemokinesis by preventing ROS activation and MAPK, PI3K/Akt, and NF-κB signaling.
- This study finds vaspin inhibit hyperglycemia-induced VSMCs proliferation.
- Vaspin attenuates HG-induced ROS production through NAPDH oxidase.
- Vaspin blocks activation of MAPK, PI3K/Akt, insulin receptor and NF-κB pathways.
- Vaspin do not stimulate the smooth muscle cells apoptosis.
Abbreviations:BSA (bovine serum albumin), DMEM (Dulbecco's modified Eagle's media), EdU (5-ethynyl-2′-deoxyuridine), H2DCFDA (2′, 7′-diclorofluorescein diacetate), IRS (insulin-receptor substrate), mM (mmol/l), PCNA (proliferating cell nuclear antigen), PI3K (phosphatidylinositol 3-kinase), PKC (protein kinase C), ROS (reactive oxygen species), TNF (tumor necrosis factor), VSMC (vascular smooth muscle cell)
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Published online: March 15, 2013
Accepted: February 13, 2013
Received in revised form: February 6, 2013
Received: October 21, 2012
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.