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Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1
Regular consumption of low-dose aspirin reduces the occurrence of colorectal, esophageal, stomach, and gastrointestinal cancers. The underlying mechanism is unknown but may be linked to inhibition of angiogenesis. Because the effective doses of aspirin are consistent with the inhibition of cyclooxyg...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102123/ https://www.ncbi.nlm.nih.gov/pubmed/27633788 http://dx.doi.org/10.1096/fj.201600530R |
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author | Rauzi, Francesca Kirkby, Nicholas S. Edin, Matthew L. Whiteford, James Zeldin, Darryl C. Mitchell, Jane A. Warner, Timothy D. |
author_facet | Rauzi, Francesca Kirkby, Nicholas S. Edin, Matthew L. Whiteford, James Zeldin, Darryl C. Mitchell, Jane A. Warner, Timothy D. |
author_sort | Rauzi, Francesca |
collection | PubMed |
description | Regular consumption of low-dose aspirin reduces the occurrence of colorectal, esophageal, stomach, and gastrointestinal cancers. The underlying mechanism is unknown but may be linked to inhibition of angiogenesis. Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid chromatography with tandem mass spectrometry analyses and immunoassays of human platelet releasates coupled with angiogenesis assays to search for the mediators of these effects. Blood or platelet-rich plasma from healthy volunteers stimulated with platelet activators produced a broad range of eicosanoids. Notably, preincubation of platelets with aspirin, but not with a P2Y(12) receptor antagonist, caused a marked reduction in the production of 11-hydroxyeicosatetraenoic acid (HETE) and 15(S)-HETE, in addition to prostanoids such as thromboxane A(2). Releasates from activated platelets caused cell migration and tube formation in cultured human endothelial cells and stimulated the sprouting of rat aortic rings in culture. These proangiogenic effects were absent when platelets were treated with aspirin but returned by coincubation with exogenous 15(S)-HETE. These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. Thus, 15(S)-HETE represents a potential target for the development of novel antiangiogenic therapeutics, and blockade of its production may provide a mechanism for the anticancer effects of aspirin.—Rauzi, F., Kirkby, N. S., Edin, M. L., Whiteford, J. Zeldin, D. C., Mitchell, J. A., Warner, T. D. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1. |
format | Online Article Text |
id | pubmed-5102123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-51021232016-11-10 Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 Rauzi, Francesca Kirkby, Nicholas S. Edin, Matthew L. Whiteford, James Zeldin, Darryl C. Mitchell, Jane A. Warner, Timothy D. FASEB J Research Regular consumption of low-dose aspirin reduces the occurrence of colorectal, esophageal, stomach, and gastrointestinal cancers. The underlying mechanism is unknown but may be linked to inhibition of angiogenesis. Because the effective doses of aspirin are consistent with the inhibition of cyclooxygenase-1 in platelets, we used liquid chromatography with tandem mass spectrometry analyses and immunoassays of human platelet releasates coupled with angiogenesis assays to search for the mediators of these effects. Blood or platelet-rich plasma from healthy volunteers stimulated with platelet activators produced a broad range of eicosanoids. Notably, preincubation of platelets with aspirin, but not with a P2Y(12) receptor antagonist, caused a marked reduction in the production of 11-hydroxyeicosatetraenoic acid (HETE) and 15(S)-HETE, in addition to prostanoids such as thromboxane A(2). Releasates from activated platelets caused cell migration and tube formation in cultured human endothelial cells and stimulated the sprouting of rat aortic rings in culture. These proangiogenic effects were absent when platelets were treated with aspirin but returned by coincubation with exogenous 15(S)-HETE. These results reveal 15(S)-HETE as a major platelet cyclooxygenase-1 product with strong proangiogenic effects. Thus, 15(S)-HETE represents a potential target for the development of novel antiangiogenic therapeutics, and blockade of its production may provide a mechanism for the anticancer effects of aspirin.—Rauzi, F., Kirkby, N. S., Edin, M. L., Whiteford, J. Zeldin, D. C., Mitchell, J. A., Warner, T. D. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1. Federation of American Societies for Experimental Biology 2016-12 2016-09-15 /pmc/articles/PMC5102123/ /pubmed/27633788 http://dx.doi.org/10.1096/fj.201600530R Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rauzi, Francesca Kirkby, Nicholas S. Edin, Matthew L. Whiteford, James Zeldin, Darryl C. Mitchell, Jane A. Warner, Timothy D. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title | Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title_full | Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title_fullStr | Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title_full_unstemmed | Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title_short | Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1 |
title_sort | aspirin inhibits the production of proangiogenic 15(s)-hete by platelet cyclooxygenase-1 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102123/ https://www.ncbi.nlm.nih.gov/pubmed/27633788 http://dx.doi.org/10.1096/fj.201600530R |
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