Angiotensin-(1-7) and angiotensin-(1-9) inhibit vascular smooth muscle cell growth and migration in vitro and vascular remodelling in vivo

Mckinney, C.A., Kennedy, S., Baillie, G.S. , Milligan, G. and Nicklin, S.A. (2015) Angiotensin-(1-7) and angiotensin-(1-9) inhibit vascular smooth muscle cell growth and migration in vitro and vascular remodelling in vivo. Atherosclerosis, 241(1), e44. (doi:10.1016/j.atherosclerosis.2015.04.158)

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Abstract

Background: Vascular smooth muscle cell(VSMC) proliferation and migration underlies the pathogenesis of atherosclerosis, vein graft failure and in-stent restenosis. Angiotensin II(AngII), acting via the AT1R, is integral in these processes. AngII is inhibited by the counter-regulatory axis of the renin angiotensin system, which is centered around the actions of angiotensin-converting-enzyme-2 and the production of Ang-(1-7) and Ang-(1-9), which act via the Mas receptor and AT2R, respectively. Here we investigated the role of Ang-(1-9) and Ang-(1-7) in primary human VSMC migration and proliferation, and in a mouse model of vascular injury. Methods: Migration was assessed via scratch assay and proliferation using the MTS-assay. Vascular injury was induced in vivo via wire injury to the left carotid artery. Ang-(1-7) and Ang-(1-9) were delivered via osmotic minipump and vascular remodeling quantified at 28 days post-injury. Results: VSMC migration and proliferation was inhibited by Ang-(1-9) and Ang-(1-7); these effects were selectively blocked by the pharmacological antagonists PD123,319 and A779, respectively, suggesting Ang-(1-9) acts via the AT2R and Ang-(1-7) via Mas. In vivo wire injury of the mouse carotid artery induced significant neointimal formation(NI) at 28 days post-injury; this was attenuated by Ang-(1-7) and Ang-(1-9) via Mas and the AT2R, respectively. Conclusion: These data demonstrate that Ang-(1-7) and Ang-(1-9) inhibit VSMC proliferation and migration in vitro and neointimal formation in vivo via the AT2R and Mas receptor, respectively. Here we demonstrate for the first time a direct biological effect of Ang-(1-9) within the vasculature. These findings highlight the potential of Ang-(1-9) and Ang-(1-7) as therapeutic agents in vascular injury.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Baillie, Professor George and Kennedy, Dr Simon and Nicklin, Professor Stuart and Mckinney, Miss Clare and Milligan, Professor Graeme
Authors: Mckinney, C.A., Kennedy, S., Baillie, G.S., Milligan, G., and Nicklin, S.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Atherosclerosis
Publisher:Elsevier Ltd.
ISSN:0021-9150
ISSN (Online):1879-1484

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