Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration

被引：5
作者：
Polzin, Amin [1 ]
Knoop, Betuel [1 ]
Boehm, Andreas [2 ]
Dannenberg, Lisa [1 ]
Zurek, Mark [1 ]
Zeus, Tobias [1 ]
Kelm, Malte [1 ]
Levkau, Bodo [3 ]
Rauch, Bernhard H. [2 ]
机构：
[1] Heinrich Heine Univ Dusseldorf, Univ Hosp Dusseldorf, Div Cardiol Pulmonol & Vasc Med, Med Fac, Dusseldorf, Germany
[2] Univ Med Greifswald, Inst Pharmakol, Abt Allgemeine Pharmakol, Felix Hausdorff Str 3, Greifswald, Germany
[3] Univ Duisburg Essen, Univ Hosp Essen, West German Heart & Vasc Ctr, Inst Pathophysiol, Essen, Germany
来源：
PHARMACOLOGY | 2018年 / 101卷 / 1-2期
关键词：
Aspirin; Sphingosine-1-phosphate; Platelet; Endothelial cell; Migration; SPHINGOSINE; 1-PHOSPHATE; ANGIOGENESIS; RELEASE; ACID;
D O I：
10.1159/000484208
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Background: Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Methods: Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor sub-types were applied. Results: S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P(1) receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P(2) or S1P(3) receptor had no effect. Conclusion: Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. (C) 2017 S, Karger AG, Basel
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页码：72 / 75
页数：4
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