Packham, IM, Watson, SP, Bicknell, R et al. (1 more author) (2014) In vivo evidence for platelet-induced physiological angiogenesis by a COX driven mechanism. PLoS One, 9 (9). e107503. e107503 - ?. ISSN 1932-6203
Abstract
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-GPIba 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Packham et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Nov 2014 11:58 |
Last Modified: | 03 Feb 2018 06:01 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0107503 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.pone.0107503 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:81311 |