Aims

Blood coagulation is one of the most important host-defending mechanisms in vivo by maintaining the blood pressure after injury. However, besides maintaining homeostasis, blood coagulation and the contributing factors are directly linked to pathological conditions, such as thromboembolism and inflammation, leading to cardiovascular diseases, among others. As anti-inflammatory drugs may reduce cardiovascular events, we hypothesized in this study that the direct thrombin inhibitor dabigatran may reduce cytokine, growth factor and chemokine expression in vitro.

Main methods

Initially, human whole blood was incubated in tubes for serum, EDTA plasma, and heparinized plasma. Furthermore, human PBMCs were isolated and incubated under different culture conditions, including the treatment with human serum or thrombin, respectively. The effect of the oral anticoagulant dabigatran on pro-inflammatory cytokines, growth factors and chemokines was investigated by ELISA.

Key findings

Conditioned serum resulted in a significant alteration of the secretome's protein levels after 24 h. However, solely ANG showed a dose-dependent increment by the addition of serum (79.8 ± 9.2 ng/mL) in comparison to baseline (0.2 ± 0.2 ng/mL), as it was in trend for thrombin treatment. Furthermore, the pre-treatment of PBMCs with different doses of dabigatran significantly lowered supernatant protein levels measured. Moreover, dabigatran was shown to decrease most notably the growth factor and chemokine levels in the PBMC's secretome that were treated with 200 ng/mL thrombin in a dose-dependent manner.

Significance

In conclusion, novel oral anticoagulants, such as dabigatran, could help to reduce not only procoagulatory effects in inflammatory conditions but could also reduce proinflammatory stimuli via reduced expression of cytokines and chemokines.

中文翻译：

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达比加群对促炎细胞因子，生长因子和趋化因子的影响-减缓凝血和炎症的恶性循环。

目的

通过维持受伤后的血压，凝血是体内最重要的宿主防御机制之一。然而，除了维持体内平衡之外，凝血和影响因素还直接与病理状况相关，例如血栓栓塞和炎症，从而导致心血管疾病。由于抗炎药可以减少心血管事件，因此我们在这项研究中假设直接凝血酶抑制剂达比加群可能在体外降低细胞因子，生长因子和趋化因子的表达。

主要方法

最初，将人类全血在试管中温育血清，EDTA血浆和肝素化血浆。此外，分离人PBMC并在不同培养条件下孵育，包括分别用人血清或凝血酶处理。通过ELISA研究了口服抗凝剂达比加群对促炎细胞因子，生长因子和趋化因子的影响。

主要发现

条件化的血清导致24小时后分泌蛋白的蛋白质水平发生重大变化。然而，与凝血酶治疗相比，与基线水平（0.2±0.2 ng / mL）相比，单独的ANG通过添加血清（79.8±9.2 ng / mL）表现出剂量依赖性的增加。此外，用不同剂量的达比加群预处理PBMC可以显着降低所测的上清蛋白水平。此外，显示达比加群显着降低了以剂量依赖性方式用200 ng / mL凝血酶处理的PBMC分泌组中的生长因子和趋化因子水平。

意义

总之，新型口服抗凝药，例如达比加群，不仅可以帮助减轻炎症条件下的促凝作用，而且还可以通过减少细胞因子和趋化因子的表达来减少促炎刺激。