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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Main Authors: Olga Porembskaya, Vsevolod Zinserling, Vladimir Tomson, Yana Toropova, Eleonora A. Starikova, Vitaliy V. Maslei, Nika I. Bulavinova, Olga V. Kirik, Marina A. Syrtsova, Leonid Laberko, Maxim I. Galchenko, Vyacheslav Kravchuk, Sergey Saiganov, Alexander Brill
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/10/5829
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author Olga Porembskaya
Vsevolod Zinserling
Vladimir Tomson
Yana Toropova
Eleonora A. Starikova
Vitaliy V. Maslei
Nika I. Bulavinova
Olga V. Kirik
Marina A. Syrtsova
Leonid Laberko
Maxim I. Galchenko
Vyacheslav Kravchuk
Sergey Saiganov
Alexander Brill
author_facet Olga Porembskaya
Vsevolod Zinserling
Vladimir Tomson
Yana Toropova
Eleonora A. Starikova
Vitaliy V. Maslei
Nika I. Bulavinova
Olga V. Kirik
Marina A. Syrtsova
Leonid Laberko
Maxim I. Galchenko
Vyacheslav Kravchuk
Sergey Saiganov
Alexander Brill
author_sort Olga Porembskaya
collection DOAJ
description 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.
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spelling doaj.art-39e463e8e9f64339aee835a09c6c1e452023-11-23T11:29:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310582910.3390/ijms23105829Neutrophils Mediate Pulmonary Artery Thrombosis In SituOlga Porembskaya0Vsevolod Zinserling1Vladimir Tomson2Yana Toropova3Eleonora A. Starikova4Vitaliy V. Maslei5Nika I. Bulavinova6Olga V. Kirik7Marina A. Syrtsova8Leonid Laberko9Maxim I. Galchenko10Vyacheslav Kravchuk11Sergey Saiganov12Alexander Brill13Cardio-Vascular Department, Mechnikov North-Western State Medical University, 191015 Saint Petersburg, RussiaInstitute of Experimental Medicine, Almazov National Medical Research Center, 197341 Saint Petersburg, RussiaScientific and Research Center, Pavlov University, 197022 Saint Petersburg, RussiaInstitute of Experimental Medicine, Almazov National Medical Research Center, 197341 Saint Petersburg, RussiaDepartment of Immunology, Institute of Experimental Medicine, 197376 Saint Petersburg, RussiaInstitute of Experimental Medicine, Almazov National Medical Research Center, 197341 Saint Petersburg, RussiaInstitute of Experimental Medicine, Almazov National Medical Research Center, 197341 Saint Petersburg, RussiaDepartment of Immunology, Institute of Experimental Medicine, 197376 Saint Petersburg, RussiaNovartis, 194362 Saint Petersburg, RussiaDepartment of General Surgery and Radiology, Pirogov Russian National Research Medical University, 117997 Moscow, RussiaDepartment of Electrical Engineering and Electrical Equipment, State Agrarian University, 196601 Saint Petersburg, RussiaCardio-Vascular Department, Mechnikov North-Western State Medical University, 191015 Saint Petersburg, RussiaCardio-Vascular Department, Mechnikov North-Western State Medical University, 191015 Saint Petersburg, RussiaInstitute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UKPulmonary 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.https://www.mdpi.com/1422-0067/23/10/5829deep vein thrombosispulmonary embolismneutrophils
spellingShingle Olga Porembskaya
Vsevolod Zinserling
Vladimir Tomson
Yana Toropova
Eleonora A. Starikova
Vitaliy V. Maslei
Nika I. Bulavinova
Olga V. Kirik
Marina A. Syrtsova
Leonid Laberko
Maxim I. Galchenko
Vyacheslav Kravchuk
Sergey Saiganov
Alexander Brill
Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
International Journal of Molecular Sciences
deep vein thrombosis
pulmonary embolism
neutrophils
title Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
title_full Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
title_fullStr Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
title_full_unstemmed Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
title_short Neutrophils Mediate Pulmonary Artery Thrombosis In Situ
title_sort neutrophils mediate pulmonary artery thrombosis in situ
topic deep vein thrombosis
pulmonary embolism
neutrophils
url https://www.mdpi.com/1422-0067/23/10/5829
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