Cargando…

Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries

We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applic...

Descripción completa

Detalles Bibliográficos
Autores principales: Hui, Sonya, Levy, Andrew S., Slack, Daniel L., Burnstein, Marcus J., Errett, Lee, Bonneau, Daniel, Latter, David, Rotstein, Ori D., Bolz, Steffen-Sebastian, Lidington, Darcy, Voigtlaender-Bolz, Julia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569583/
https://www.ncbi.nlm.nih.gov/pubmed/26367262
http://dx.doi.org/10.1371/journal.pone.0138142
_version_ 1782390064944250880
author Hui, Sonya
Levy, Andrew S.
Slack, Daniel L.
Burnstein, Marcus J.
Errett, Lee
Bonneau, Daniel
Latter, David
Rotstein, Ori D.
Bolz, Steffen-Sebastian
Lidington, Darcy
Voigtlaender-Bolz, Julia
author_facet Hui, Sonya
Levy, Andrew S.
Slack, Daniel L.
Burnstein, Marcus J.
Errett, Lee
Bonneau, Daniel
Latter, David
Rotstein, Ori D.
Bolz, Steffen-Sebastian
Lidington, Darcy
Voigtlaender-Bolz, Julia
author_sort Hui, Sonya
collection PubMed
description We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.
format Online
Article
Text
id pubmed-4569583
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-45695832015-09-18 Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries Hui, Sonya Levy, Andrew S. Slack, Daniel L. Burnstein, Marcus J. Errett, Lee Bonneau, Daniel Latter, David Rotstein, Ori D. Bolz, Steffen-Sebastian Lidington, Darcy Voigtlaender-Bolz, Julia PLoS One Research Article We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study. Public Library of Science 2015-09-14 /pmc/articles/PMC4569583/ /pubmed/26367262 http://dx.doi.org/10.1371/journal.pone.0138142 Text en © 2015 Hui et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Hui, Sonya
Levy, Andrew S.
Slack, Daniel L.
Burnstein, Marcus J.
Errett, Lee
Bonneau, Daniel
Latter, David
Rotstein, Ori D.
Bolz, Steffen-Sebastian
Lidington, Darcy
Voigtlaender-Bolz, Julia
Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title_full Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title_fullStr Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title_full_unstemmed Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title_short Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries
title_sort sphingosine-1-phosphate signaling regulates myogenic responsiveness in human resistance arteries
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569583/
https://www.ncbi.nlm.nih.gov/pubmed/26367262
http://dx.doi.org/10.1371/journal.pone.0138142
work_keys_str_mv AT huisonya sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT levyandrews sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT slackdaniell sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT burnsteinmarcusj sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT errettlee sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT bonneaudaniel sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT latterdavid sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT rotsteinorid sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT bolzsteffensebastian sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT lidingtondarcy sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries
AT voigtlaenderbolzjulia sphingosine1phosphatesignalingregulatesmyogenicresponsivenessinhumanresistancearteries