This work was supported by a grant from the Medical Research Council, UK (MR/K012789/1). Additional information can be downloaded from the publisher's websitePeer reviewedPublisher PD

Gibson, George

Greig, Fiona H

Kennedy, Simon

Nixon, Graeme F

Ramos, Joe W

Journal of the American Heart Association

English

This work was supported by a grant from the Medical Research Council, UK (MR/K012789/1). Additional information can be downloaded from the publisher's websitePeer reviewe

The Open University

PEA‐15 (Phosphoprotein Enriched in Astrocytes 15) Is a Protective Mediator in the Vasculature and Is Regulated During Neointimal Hyperplasia

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

Greig, Fiona H.

Ramos, Joe W.

Nixon, Graeme F.

Enlighten: Publications

PEA-15 (phosphoprotein enriched in astrocytes 15) is a protective mediator in the vasculature and is regulated during neointimal hyperplasia


            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
              ERK
              1/2‐dependent proliferation in vitro.
              PEA
              ‐15 acts as a cytoplasmic anchor for
              ERK
              1/2, preventing nuclear localization and thereby reducing
              ERK
              1/2‐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,
              ERK
              1/2 had increased nuclear translocation and increased basal
              ERK
              1/2‐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.
            
          </jats:sec

PEA‐15 (Phosphoprotein Enriched in Astrocytes 15) Is a Protective Mediator in the Vasculature and Is Regulated During Neointimal Hyperplasia

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