Cardio-Vascular Department, Mechnikov North-Western State Medical University, 191015 Saint Petersburg, Russia.
Institute of Experimental Medicine, Almazov National Medical Research Center, 197341 Saint Petersburg, Russia.
Int J Mol Sci. 2022 May 23;23(10):5829. doi: 10.3390/ijms23105829.
Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.
肺栓塞是一种危及生命的疾病，可导致呼吸功能不全和死亡。阻塞肺动脉（PA）分支的血栓通常被认为来源于深静脉（通常在腿部）中的血栓。然而，越来越多的证据表明，在没有先前深静脉血栓形成（DVT）的情况下，肺部血管的阻塞也可能发生。在这项工作中，我们使用了 Wistar 大鼠的下腔静脉（IVC）完全结扎模型来研究在所有血栓物质从外周静脉迁移的途径都被阻断的情况下，PA 血栓形成的可能性和机制。我们证明，中性粒细胞计数正常和减少的大鼠均在 IVC 中形成血栓，尽管中性粒细胞减少症导致血栓大小显著减小，并使血栓内部的新鲜纤维蛋白向成熟纤维蛋白和结缔组织转变。在大多数中性粒细胞计数正常的 DVT 大鼠的 PA 分支中发现大量纤维蛋白沉积，但在中性粒细胞减少症动物中均未发现。中性粒细胞消融也消除了肺损伤的宏观迹象。总之，这些结果表明，在 DVT 情况下，通过需要局部中性粒细胞募集的机制，肺血管中的血栓可以原位形成。
