Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
Vaspin inhibits HG-induced VSMCs proliferation and chemokinesis by preventing ROS
activation and MAPK, PI3K/Akt, and NF-κB signaling.
Highlights
- 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.
Keywords
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)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Preventing macrovascular disease in patients with type 2 diabetes mellitus.Am J Cardiovasc Drugs. 2003; 3: 283-297
- Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels.Diabetes. 2001; 50: 851-860
- Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I.Circulation. 2003; 108: 1527-1532
- Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity.Proc Natl Acad Sci U S A. 2005; 102: 10610-10615
- Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes.Biochem Biophys Res Commun. 2006; 339: 430-436
- Short-term continuous subcutaneous insulin infusion decreases the plasma vaspin levels in patients with type 2 diabetes mellitus concomitant with improvement in insulin sensitivity.Eur J Endocrinol. 2011; 164: 905-910
- Serum levels of vaspin and visfatin in patients with coronary artery disease-Kozani study.Clin Chim Acta. 2011; 412: 48-52
- Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris.Clin Chem Lab Med. 2011; 49: 1547-1554
- Vaspin serum concentrations in patients with carotid stenosis.Atherosclerosis. 2009; 204: 262-266
- Serum vaspin levels in type 2 diabetic women in relation to microvascular complications.Eur J Endocrinol. 2009; 160: 65-70
- Calorie control increased vaspin levels of serum and periepididymal adipose tissue in diet-induced obese rats in association with serum free fatty acid and tumor necrosis factor alpha.Chin Med J (Engl). 2010; 123: 936-941
- Vaspin prevents TNF-alpha-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-kappaB and PKCtheta activation in cultured rat vascular smooth muscle cells.Pharmacol Res. 2011; 64: 493-500
- A novel adipocytokine, vaspin inhibits platelet-derived growth factor-BB-induced migration of vascular smooth muscle cells.Biochem Biophys Res Commun. 2012; 423: 844-849
- Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway.Biochem Biophys Res Commun. 2011; 413: 264-269
- MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration.Blood. 2007; 109: 987-994
- Puerarin attenuates high-glucose-and diabetes-induced vascular smooth muscle cell proliferation by blocking PKCbeta2/Rac1-dependent signaling.Free Radic Biol Med. 2010; 48: 471-482
- Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR.J Am Soc Hypertens. 2011; 5: 137-153
- Grape seed proanthocyanidins attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3-kinase-dependent signaling pathways.J Cell Physiol. 2010; 223: 713-726
- Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells.J Biol Chem. 2010; 285: 15682-15695
- NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities.Diabetes Care. 2008; 31: S170-S180
- NADPH oxidases are responsible for the failure of nitric oxide to inhibit migration of smooth muscle cells exposed to high glucose.Free Radic Biol Med. 2009; 47: 1578-1583
- Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats.J Atheroscler Thromb. 2007; 14: 235-244
- Impact of atorvastatin on serum vaspin levels in hypercholesterolemic patients with moderate cardiovascular risk.Regul Pept. 2011; 170: 57-61
- Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II.Arterioscler Thromb Vasc Biol. 2005; 25: 1142-1147
- Insulin receptor substrates-1 and -2 are both depleted but via different mechanisms after down-regulation of glucose transport in rat adipocytes.Endocrinology. 2005; 146: 3044-3051
- An E2F1-dependent gene expression program that determines the balance between proliferation and cell death.Cancer Cell. 2008; 13: 11-22
- Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species.J Biol Chem. 2008; 283: 7864-7876
- Chemokines: inflammatory mediators of atherosclerosis.Arch Physiol Biochem. 2006; 112: 229-238
- CD73/ecto-5′-nucleotidase protects against vascular inflammation and neointima formation.Circulation. 2006; 113: 2120-2127
- Vaspin can not inhibit TNF-alpha-induced inflammation of human umbilical vein endothelial cells.J Vet Med Sci. 2009; 71: 1201-1207
Article info
Publication history
Published online: March 15, 2013
Accepted:
February 13,
2013
Received in revised form:
February 6,
2013
Received:
October 21,
2012
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
