Endothelin-1 activates ETA receptors on human vascular smooth muscle cells to yield proteoglycans with increased binding to LDL

Ballinger, M. L., Ivey, M. E., Osman, N., Thomas, W. G. and Little, P. J. (2009) Endothelin-1 activates ETA receptors on human vascular smooth muscle cells to yield proteoglycans with increased binding to LDL. Atherosclerosis, 205 2: 451-457. doi:10.1016/j.atherosclerosis.2009.01.024


Author Ballinger, M. L.
Ivey, M. E.
Osman, N.
Thomas, W. G.
Little, P. J.
Title Endothelin-1 activates ETA receptors on human vascular smooth muscle cells to yield proteoglycans with increased binding to LDL
Journal name Atherosclerosis   Check publisher's open access policy
ISSN 0021-9150
Publication date 2009-08
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.atherosclerosis.2009.01.024
Open Access Status
Volume 205
Issue 2
Start page 451
End page 457
Total pages 7
Place of publication Ireland
Publisher Elsevier Ireland Ltd
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060110 Receptors and Membrane Biology
110201 Cardiology (incl. Cardiovascular Diseases)
Abstract Objective: Lipid retention in the vessel wall by glycosaminoglycan (GAG) chains on chondroitin/dermatan sulfate proteoglycans synthesized by vascular smooth muscle cells (VSMC) have recently been established as an early event in human coronary artery atherosclerosis. GAG structure can be altered by growth factors resulting in enhanced binding to low density lipoprotein (LDL). The aim of this study was to determine if proteoglycans produced by endothelin-1 treated VSMCs had increased binding to human LDL, to examine the effect of endothelin-1 on the synthesis and structure of proteoglycans and to elucidate the signalling pathway. Methods and results: Endothelin-1 stimulated an increase in [S-35]sulfate and [(3) H]glucosamine incorporation into proteoglycans produced by human VSMC. The increase was due to an increase in GAG chain size assessed by SDS-PAGE and size exclusion chromatography. Increased radiolabel incorporation was inhibited by an ETA but not an ETB receptor antagonist. Endothelin-1 stimulated an increase in the 6:4 position sulfation ratio on the disaccharides of the GAG chains, an effect that was blocked by bosentan. The EGF receptor antagonist AG1478 did not affect the increase in GAG size mediated by endothelin-1. Inhibition of protein kinase C (PKC) with GF109203X or down regulation by PMA pre-treatment attenuated the effect of endothelin-1 on GAG synthesis. Conclusion: These data demonstrate that endothelin-1 stimulates changes in GAG chain structure that increase binding to LDL This action of endothelin-1 may represent a new target for the prevention of lipid binding within the vascular wall and the associated complications resulting from this interaction. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Keyword Endothelin-1
Vascular smooth muscle cells
Proteoglycans
Glycosaminoglycans
Lipid binding
LOW-DENSITY-LIPOPROTEIN
PROTEIN-KINASE-C
ANGIOTENSIN-II
ATHEROSCLEROSIS
Proliferation
ATHEROGENESIS
BIOSYNTHESIS
EXPRESSION
RETENTION
MIGRATION
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Thu, 17 Sep 2009, 10:04:20 EST by Cameron Harris on behalf of School of Biomedical Sciences