The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection.
The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection.
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Matrikine 乙酰化脯氨酸-甘氨酸-脯氨酸与血管炎症和急性心脏排斥反应相关。
DOI：
10.1038/s41598-017-07610-0
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发表时间：
2017
影响因子：
4.6
通讯作者：
Gaggar,Amit
中科院分区：
文献类型：
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作者：
Payne,GregoryA;Li,Jindong;Xu,Xin;Jackson,Patricia;Qin,Hongwei;Pollock,DavidM;Wells,JMichael;Oparil,Suzanne;Leesar,Massoud;Patel,RakeshP;Blalock,JEdwin;Gaggar,Amit
细胞外基质（ECM）是一种动态的、生物活性的结构，对器官的发育、结构和功能至关重要。ECM的过度重塑是包括血管疾病在内的多种炎症性疾病的标志。内皮素-1（ET 1）的合成被认为是促进心血管疾病，包括急性心脏移植排斥反应;然而，ECM衍生的趋化因子（基质因子）对血管炎症的贡献仍然知之甚少。本文报道了基质因子乙酰化的Pro-Gly-Pro（PGP）通过激活内皮细胞CXC趋化因子受体2（CXCR 2）和产生内皮素-1（ET-1）刺激血管炎症反应。作为假设的证据，我们证明冠状动脉PGP水平与循环内皮素-1和心脏移植患者的急性排斥反应相关（敏感性为100%，特异性为86%）。这些发现确立了PGP作为心血管疾病中的新型介质，并暗示生物活性基质片段作为在进行性血管炎症传播的许多病症中潜在活性的未被充分认识的药剂。
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 bothin vitroandin 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.