Neutrophils Mediate Pulmonary Artery Thrombosis In Situ

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 occ...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-05, Vol.23 (10), p.5829
Main Authors: Porembskaya, Olga, Zinserling, Vsevolod, Tomson, Vladimir, Toropova, Yana, Starikova, Eleonora A, Maslei, Vitaliy V, Bulavinova, Nika I, Kirik, Olga V, Syrtsova, Marina A, Laberko, Leonid, Galchenko, Maxim I, Kravchuk, Vyacheslav, Saiganov, Sergey, Brill, Alexander
Format: Article
Language:English
Subjects:
Ablation
Animal models
Animals
Blood clots
Blood coagulation
Blood platelets
Connective tissue
Cyanosis
Embolism
Embolisms
Endothelium
Fibrin
Hypotheses
Ischemia
Leukocytes (neutrophilic)
Lung
Lungs
Mortality
Neutropenia
Neutrophils
Occlusion
Pulmonary arteries
Pulmonary Artery
Pulmonary embolisms
Rats
Rats, Wistar
Surgery
Thrombosis
Veins
Veins & arteries
Venous Thrombosis - etiology
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23105829