The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
Abstract 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 car...
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Nature Portfolio
2017
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oai:doaj.org-article:a02a41bb53f14b3b8aaea863666146da2021-12-02T16:06:31ZThe Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection10.1038/s41598-017-07610-02045-2322https://doaj.org/article/a02a41bb53f14b3b8aaea863666146da2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07610-0https://doaj.org/toc/2045-2322Abstract 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.Gregory A. PayneJindong LiXin XuPatricia JacksonHongwei QinDavid M. PollockJ. Michael WellsSuzanne OparilMassoud LeesarRakesh P. PatelJ. Edwin BlalockAmit GaggarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Gregory A. Payne Jindong Li Xin Xu Patricia Jackson Hongwei Qin David M. Pollock J. Michael Wells Suzanne Oparil Massoud Leesar Rakesh P. Patel J. Edwin Blalock Amit Gaggar The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection |
| description |
Abstract 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. |
| format |
article |
| author |
Gregory A. Payne Jindong Li Xin Xu Patricia Jackson Hongwei Qin David M. Pollock J. Michael Wells Suzanne Oparil Massoud Leesar Rakesh P. Patel J. Edwin Blalock Amit Gaggar |
| author_facet |
Gregory A. Payne Jindong Li Xin Xu Patricia Jackson Hongwei Qin David M. Pollock J. Michael Wells Suzanne Oparil Massoud Leesar Rakesh P. Patel J. Edwin Blalock Amit Gaggar |
| author_sort |
Gregory A. Payne |
| title |
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_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_sort |
matrikine acetylated proline-glycine-proline couples vascular inflammation and acute cardiac rejection |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a02a41bb53f14b3b8aaea863666146da |
| work_keys_str_mv |
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