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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 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Payne GA,Li J,Xu X,Jackson P,Qin H,Pollock DM,Wells JM,Oparil S,Leesar M,Patel RP,Blalock JE,Gaggar A

doi

10.1038/s41598-017-07610-0

subject

Has Abstract

pub_date

2017-08-08 00:00:00

pages

7563

issue

1

issn

2045-2322

pii

10.1038/s41598-017-07610-0

journal_volume

7

pub_type

杂志文章

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