G protein-coupled receptor 35 mediates human saphenous vein vascular smooth muscle cell migration and endothelial cell proliferation

McCallum, J. E., Mackenzie, A. E., Divorty, N., Clarke, C., Delles, C. , Milligan, G. and Nicklin, S. A. (2016) G protein-coupled receptor 35 mediates human saphenous vein vascular smooth muscle cell migration and endothelial cell proliferation. Journal of Vascular Research, 52(6), pp. 383-395. (doi:10.1159/000444754) (PMID:27064272) (PMCID:PMC4959467)

[img]
Preview
Text
116605.pdf - Published Version
Available under License Creative Commons Attribution.

397kB

Abstract

Vascular smooth muscle cell (VSMC) migration and proliferation is central to neointima formation in vein graft failure following coronary artery bypass. However, there are currently no pharmacological interventions that prevent vein graft failure through intimal occlusion. It is hence a therapeutic target. Here, we investigated the contribution of GPR35 to human VSMC and endothelial cell (EC) migration using a scratch wound assay and proliferation using MTS and BrdU assays in in vitro models using recently characterized human GPR35 ortholog selective small molecule agonists and antagonists. Real-time-PCR studies showed GPR35 to be robustly expressed in human VSMC and EC. Stimulation of GPR35 with either the human-selective agonist pamoic acid, or the reference agonist zaprinast, promoted VSMC migration in a scratch wound assay. These effects were blocked by co-incubation with either of the human GPR35 specific antagonists CID-2745687 or ML-145. These GPR35 mediated effects were produced by inducing alterations in the actin cytoskeleton via the RhoA/Rho kinase signaling axis. Additionally, the agonist ligands stimulated a proliferative response in ECs. These studies highlight the potential that small molecules that stimulate or block GPR35 activity can modulate vascular proliferation and migration. These data suggest GPR35 as a translational therapeutic target in vascular remodeling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nicklin, Professor Stuart and Clarke, Dr Carolyn and Milligan, Professor Graeme and Delles, Professor Christian and Mackenzie, Miss Amanda
Authors: McCallum, J. E., Mackenzie, A. E., Divorty, N., Clarke, C., Delles, C., Milligan, G., and Nicklin, S. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Vascular Research
Publisher:Karger
ISSN:1018-1172
ISSN (Online):1423-0135
Published Online:12 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Journal of Vascular Research 52(6):383-395
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record