![](/images/graphics-bg.png)
Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice
Joint Authors
Münzel, Thomas
Brandt, Moritz
Garlapati, Venkata
Molitor, Michael
Kossmann, Sabine
Schäfer, Katrin
Karbach, Susanne Helena
Giokoglu, Eleni
Bochenek, Madgalena L.
Hobohm, Lukas
Schönfelder, Tanja
Wenzel, Philip
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-06-10
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Pulmonary embolism (PE) results from deep vein thrombosis (DVT) and can lead to chronic thromboembolic pulmonary hypertension (CTEPH) involving vascular dysfunction.
Mechanisms are incompletely understood, in part due to lack of mouse models.
We induced PE in C57BL/6 mice by intravenous injection of thrombin (166 U/kg BW), confirmed by a sudden bradycardia, bradypnea, and an increase in pulmonary artery (PA) pressure observed by high-frequency ultrasound.
While symptoms resolved rapidly after single thrombin application, repeated PEs resulted in sustained PA-pressure increase, increased PA superoxide formation assessed by oxidative fluorescent microtopography, increased PA gp91phox expression, and endothelial dysfunction assessed by isometric tension studies of isolated PA segments after 24 hours.
DVT was modeled in C57BL/6 mice by ligation of the inferior vena cava (IVC).
Importantly, small pulmonary emboli could be detected along with a mild phenotype of PA endothelial dysfunction and oxidative stress in the absence of PA-pressure elevation.
mRNA expression of plasminogen activator inhibitor-1 was increased in PAs of mice with recurrent PE after repetitive thrombin injections and to a lesser extent in DVT mice.
In summary, our data suggest that PA endothelial dysfunction, induced by gp91phox-derived ROS, is an early event upon repetitive PE.
This phenomenon might help to elucidate the mechanisms of PA dysfunction in the pathogenesis of CTEPH.
American Psychological Association (APA)
Brandt, Moritz& Giokoglu, Eleni& Garlapati, Venkata& Bochenek, Madgalena L.& Molitor, Michael& Hobohm, Lukas…[et al.]. 2018. Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1210931
Modern Language Association (MLA)
Brandt, Moritz…[et al.]. Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-10.
https://search.emarefa.net/detail/BIM-1210931
American Medical Association (AMA)
Brandt, Moritz& Giokoglu, Eleni& Garlapati, Venkata& Bochenek, Madgalena L.& Molitor, Michael& Hobohm, Lukas…[et al.]. Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-10.
https://search.emarefa.net/detail/BIM-1210931
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1210931