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Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)

The plasma level of LPA (lysophosphatidic acid) (200–600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that atte...

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Autores principales: Park, Eun Young, Kazlauskas, Andrius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392100/
https://www.ncbi.nlm.nih.gov/pubmed/22639801
http://dx.doi.org/10.1042/BSR20120033
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author Park, Eun Young
Kazlauskas, Andrius
author_facet Park, Eun Young
Kazlauskas, Andrius
author_sort Park, Eun Young
collection PubMed
description The plasma level of LPA (lysophosphatidic acid) (200–600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.
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spelling pubmed-33921002012-07-12 Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA) Park, Eun Young Kazlauskas, Andrius Biosci Rep Original Paper The plasma level of LPA (lysophosphatidic acid) (200–600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA. Portland Press Ltd. 2012-06-28 2012-08-01 /pmc/articles/PMC3392100/ /pubmed/22639801 http://dx.doi.org/10.1042/BSR20120033 Text en © 2012 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited
spellingShingle Original Paper
Park, Eun Young
Kazlauskas, Andrius
Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title_full Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title_fullStr Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title_full_unstemmed Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title_short Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA)
title_sort primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (lpa)
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392100/
https://www.ncbi.nlm.nih.gov/pubmed/22639801
http://dx.doi.org/10.1042/BSR20120033
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