Greig, F. H., Kennedy, S. , Gibson, G., Ramos, J. W. and Nixon, G. F. (2017) PEA-15 (phosphoprotein enriched in astrocytes 15) is a protective mediator in the vasculature and is regulated during neointimal hyperplasia. Journal of the American Heart Association, 6(9), e006936. (doi: 10.1161/JAHA.117.006936) (PMID:28893763) (PMCID:PMC5634313)
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Abstract
Background: Neointimal hyperplasia following angioplasty occurs via vascular smooth muscle cell proliferation. The mechanisms involved are not fully understood but include mitogen‐activated protein kinases ERK1/2 (extracellular signal–regulated kinases 1 and 2). We recently identified the intracellular mediator PEA‐15 (phosphoprotein enriched in astrocytes 15) in vascular smooth muscle cells as a regulator of ERK1/2‐dependent proliferation in vitro. PEA‐15 acts as a cytoplasmic anchor for ERK1/2, preventing nuclear localization and thereby reducing ERK1/2‐dependent gene expression. The aim of the current study was to examine the role of PEA‐15 in neointimal hyperplasia in vivo. Method and Results: Mice deficient in PEA‐15 or wild‐type mice were subjected to wire injury of the carotid artery. In uninjured arteries from PEA‐15–deficient mice, ERK1/2 had increased nuclear translocation and increased basal ERK1/2‐dependent transcription. Following wire injury, arteries from PEA‐15–deficient mice developed neointimal hyperplasia at an increased rate compared with wild‐type mice. This occurred in parallel with an increase in a proliferative marker and vascular smooth muscle cell proliferation. In wild‐type mice, PEA‐15 expression was decreased in vascular smooth muscle cells at an early stage before any increase in intima:media ratio. This regulation of PEA‐15 expression following injury was also observed in an ex vivo human model of hyperplasia. Conclusions: These results indicate, for the first time, a novel protective role for PEA‐15 against inappropriate vascular proliferation. PEA‐15 expression may also be repressed during vascular injury, suggesting that maintenance of PEA‐15 expression is a novel therapeutic target in vascular disease.
| Item Type: | Articles |
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| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kennedy, Professor Simon |
| Authors: | Greig, F. H., Kennedy, S., Gibson, G., Ramos, J. W., and Nixon, G. F. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Life Sciences |
| Journal Name: | Journal of the American Heart Association |
| Publisher: | American Heart Association |
| ISSN: | 2047-9980 |
| ISSN (Online): | 2047-9980 |
| Published Online: | 11 September 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Journal of the American Heart Association 6(9): e006936 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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