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)
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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 |
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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, Dr 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 > School of Cardiovascular & Metabolic Health |
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 |
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