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The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection

The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascul...

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Autores principales: Payne, Gregory A., Li, Jindong, Xu, Xin, Jackson, Patricia, Qin, Hongwei, Pollock, David M., Wells, J. Michael, Oparil, Suzanne, Leesar, Massoud, Patel, Rakesh P., Blalock, J. Edwin, Gaggar, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548740/
https://www.ncbi.nlm.nih.gov/pubmed/28790330
http://dx.doi.org/10.1038/s41598-017-07610-0
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author Payne, Gregory A.
Li, Jindong
Xu, Xin
Jackson, Patricia
Qin, Hongwei
Pollock, David M.
Wells, J. Michael
Oparil, Suzanne
Leesar, Massoud
Patel, Rakesh P.
Blalock, J. Edwin
Gaggar, Amit
author_facet Payne, Gregory A.
Li, Jindong
Xu, Xin
Jackson, Patricia
Qin, Hongwei
Pollock, David M.
Wells, J. Michael
Oparil, Suzanne
Leesar, Massoud
Patel, Rakesh P.
Blalock, J. Edwin
Gaggar, Amit
author_sort Payne, Gregory A.
collection PubMed
description The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo. As a proof of hypothesis, we demonstrate that coronary PGP levels associate with both circulating endothelin-1 and acute rejection in cardiac transplant patients (sensitivity of 100% and specificity of 86%). These findings establish PGP as a novel mediator in cardiovascular disease, and implicate bioactive matrix fragments as underappreciated agents potentially active in numerous conditions propagated by progressive vascular inflammation.
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spelling pubmed-55487402017-08-09 The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection Payne, Gregory A. Li, Jindong Xu, Xin Jackson, Patricia Qin, Hongwei Pollock, David M. Wells, J. Michael Oparil, Suzanne Leesar, Massoud Patel, Rakesh P. Blalock, J. Edwin Gaggar, Amit Sci Rep Article The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo. As a proof of hypothesis, we demonstrate that coronary PGP levels associate with both circulating endothelin-1 and acute rejection in cardiac transplant patients (sensitivity of 100% and specificity of 86%). These findings establish PGP as a novel mediator in cardiovascular disease, and implicate bioactive matrix fragments as underappreciated agents potentially active in numerous conditions propagated by progressive vascular inflammation. Nature Publishing Group UK 2017-08-08 /pmc/articles/PMC5548740/ /pubmed/28790330 http://dx.doi.org/10.1038/s41598-017-07610-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Payne, Gregory A.
Li, Jindong
Xu, Xin
Jackson, Patricia
Qin, Hongwei
Pollock, David M.
Wells, J. Michael
Oparil, Suzanne
Leesar, Massoud
Patel, Rakesh P.
Blalock, J. Edwin
Gaggar, Amit
The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title_full The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title_fullStr The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title_full_unstemmed The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title_short The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
title_sort matrikine acetylated proline-glycine-proline couples vascular inflammation and acute cardiac rejection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548740/
https://www.ncbi.nlm.nih.gov/pubmed/28790330
http://dx.doi.org/10.1038/s41598-017-07610-0
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