In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.

We sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C:F) of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longit...

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Main Authors: Ian M Packham, Steve P Watson, Roy Bicknell, Stuart Egginton
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4169573?pdf=render
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spelling doaj-4863435a823844db929ec340759831632020-11-25T02:06:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10750310.1371/journal.pone.0107503In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.Ian M PackhamSteve P WatsonRoy BicknellStuart EggintonWe sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C:F) of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longitudinal splitting by chronic hyperaemia. Platelet depletion was achieved by anti-GPIbα antibody treatment. Sprouting induced a significant increase in C:F (1.42±0.02 vs. contralateral 1.29±0.02, P<0.001) that was abolished by platelet depletion, while the significant C:F increase caused by splitting (1.40±0.03 vs. control 1.28±0.03, P<0.01) was unaffected. Granulocyte/monocyte depletion showed this response was not immune-regulated. VEGF overexpression failed to rescue angiogenesis following platelet depletion, suggesting the mechanism is not simply reliant on growth factor release. Sprouting occurred normally following antibody-induced GPVI shedding, suggesting platelet activation via collagen is not involved. BrdU pulse-labelling showed no change in the proliferative potential of cells associated with capillaries after platelet depletion. Inhibition of platelet activation by acetylsalicylic acid abolished sprouting, but not splitting angiogenesis, paralleling the response to platelet depletion. We conclude that platelets differentially regulate mechanisms of angiogenesis in vivo, likely via COX signalling. Since endothelial proliferation is not impaired, we propose a link between COX1 and induction of endothelial migration.http://europepmc.org/articles/PMC4169573?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Ian M Packham
Steve P Watson
Roy Bicknell
Stuart Egginton
spellingShingle Ian M Packham
Steve P Watson
Roy Bicknell
Stuart Egginton
In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
PLoS ONE
author_facet Ian M Packham
Steve P Watson
Roy Bicknell
Stuart Egginton
author_sort Ian M Packham
title In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
title_short In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
title_full In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
title_fullStr In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
title_full_unstemmed In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism.
title_sort in vivo evidence for platelet-induced physiological angiogenesis by a cox driven mechanism.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description We sought to determine a role for platelets in in vivo angiogenesis, quantified by changes in the capillary to fibre ratio (C:F) of mouse skeletal muscle, utilising two distinct forms of capillary growth to identify differential effects. Capillary sprouting was induced by muscle overload, and longitudinal splitting by chronic hyperaemia. Platelet depletion was achieved by anti-GPIbα antibody treatment. Sprouting induced a significant increase in C:F (1.42±0.02 vs. contralateral 1.29±0.02, P<0.001) that was abolished by platelet depletion, while the significant C:F increase caused by splitting (1.40±0.03 vs. control 1.28±0.03, P<0.01) was unaffected. Granulocyte/monocyte depletion showed this response was not immune-regulated. VEGF overexpression failed to rescue angiogenesis following platelet depletion, suggesting the mechanism is not simply reliant on growth factor release. Sprouting occurred normally following antibody-induced GPVI shedding, suggesting platelet activation via collagen is not involved. BrdU pulse-labelling showed no change in the proliferative potential of cells associated with capillaries after platelet depletion. Inhibition of platelet activation by acetylsalicylic acid abolished sprouting, but not splitting angiogenesis, paralleling the response to platelet depletion. We conclude that platelets differentially regulate mechanisms of angiogenesis in vivo, likely via COX signalling. Since endothelial proliferation is not impaired, we propose a link between COX1 and induction of endothelial migration.
url http://europepmc.org/articles/PMC4169573?pdf=render
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