Regulation of cardiomyocyte full-length tissue factor expression and microparticle release under inflammatory conditions in vitro
Regulation of cardiomyocyte full-length tissue factor expression and microparticle release under inflammatory conditions in vitro
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DOI：
10.1111/j.1538-7836.2009.03323.x
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发表时间：
2009-05-01
影响因子：
10.4
通讯作者：
Rauch, U.
中科院分区：
文献类型：
--
作者：
Antoniak, S.;Boltzen, U.;Rauch, U.
背景：心肌炎症与循环微粒（MPs）和促凝能力的增加有关。目的：我们确定急性炎症是否与心肌细胞全长组织因子（flTF）表达改变和促凝性增加有关。方法：本研究检测了小鼠心肌细胞（HL-1） flTF表达的转录调控。此外，我们还评估了HL-1细胞产生MPs的情况及其通过人工内皮细胞扩散的能力。结果：当c-Jun n -末端激酶（JNK）被抑制时，组成型和肿瘤坏死因子- α (tnf - α)诱导的HL-1 flTF表达降低。组织因子（TF）阳性的促凝MPs在tnf - α的作用下从HL-1细胞释放。JNK抑制增强了HL-1细胞中MPs的释放，但不影响mp相关的TF活性。MP的产生依赖于RhoA的激活，并与肌动蛋白细胞骨架的重组有关。tnf - α治疗后发现hl -1来源的MPs通过内皮单层扩散增加。扩散的增加不仅依赖于tnf - α，还依赖于hl -1释放的介质。结论：JNK可调控HL-1细胞全长TF的表达。tnf - α诱导的促凝性增加是通过rhoa依赖性释放含fltf的MPs介导的。这些MPs能够通过HL-1细胞附近的内皮屏障扩散，并增加细胞外内皮空间的促凝性。心肌细胞似乎是含有fltf的促凝MPs的可能来源。
Background: Myocardial inflammation is associated with an increase in circulating microparticles (MPs) and procoagulability. Objectives: We determined whether acute inflammation was associated with altered full-length tissue factor (flTF) expression and increased procoagulability in cardiomyocytic cells. Methods: This study examined the transcriptional regulation of flTF expression in murine cardiomyocytic (HL-1) cells. Also, the generation of MPs by HL-1 cells and their ability to diffuse through an artificial endothelium was evaluated. Results: Constitutive and tumor necrosis factor-alpha (TNF-alpha)-induced flTF expression of HL-1 was reduced when c-Jun N-terminal kinase (JNK) was inhibited. Tissue factor (TF)-positive procoagulant MPs were released from HL-1 cells in response to TNF-alpha. JNK inhibition potentiated the release of MPs from HL-1 cells without affecting MP-associated TF activity. MP generation was dependent on RhoA activation and associated with a reorganization of the actin cytoskeleton. Increased diffusion of HL-1-derived MPs through an endothelial monolayer was found after TNF-alpha treatment. The increased diffusion was dependent not only on TNF-alpha but also on HL-1-released mediators. Conclusions: Full-length TF expression in HL-1 cells was regulated through JNK. The TNF-alpha-induced increase in procoagulability was mediated through RhoA-dependent release of flTF-bearing MPs. These MPs were able to diffuse through an endothelial barrier adjacent to HL-1 cells and increased the procoagulability of the extracellular endothelial space. Cardiomyocytes seem to be a likely source of flTF-bearing procoagulant MPs.