The effect of Monoamine oxidase A inhibition on experimentally induced pulmonary arterial hypertension
| العنوان: | The effect of Monoamine oxidase A inhibition on experimentally induced pulmonary arterial hypertension |
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| المؤلفون: | Anton Vonk-Noordegraaf, Eva Peters, Stine Andersen, Xiao-Qing Sun, Frances S. de Man, Willen Van Der Laarse, Denielli da Silva Goncalves Bos, Harm Jan Bogaard, Ingrid Schalij |
| المساهمون: | Pulmonary medicine, Physiology, ACS - Pulmonary hypertension & thrombosis, APH - Quality of Care |
| المصدر: | Sun, X-Q, Peters, E, Schalij, I, Andersen, S, Bos, D D S G, Vonk-Noordegraaf, A, De Man, F S, Van der Laarse, W & Bogaard, H J 2018, ' The effect of Monoamine oxidase A inhibition on experimentally induced pulmonary arterial hypertension ', European Respiratory Journal, vol. 52 . https://doi.org/10.1183/13993003.congress-2018.PA3072 European Respiratory Journal, 52. European Respiratory Society |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, Lung, biology, business.industry, Hypoxia (medical), medicine.disease, 03 medical and health sciences, 030104 developmental biology, Blood pressure, medicine.anatomical_structure, Afterload, Internal medicine, Heart failure, Clorgyline, biology.protein, Cardiology, Medicine, Monoamine oxidase A, medicine.symptom, business |
| الوصف: | Background: Reactive oxygen species (ROS) play a crucial role in the pathogenesis of pulmonary arterial hypertension (PAH). Monoamine oxidases (MAO), a class of enzymes located in the outer mitochondrial membrane, are important ROS sources. Increased MAO-A expression in endothelial cells and cardiomyocytes was found to contribute to vascular dysfunction and left heart failure. MAO-A inhibition can improve vascular dysfunction and heart failure. Collectively, given the effects of MAO-A on both vascular and cardiac function, we hypothesized that inhibition of MAO-A can be used to treat PAH. Methods: PAH was induced in male Sprague-Dawley rats by a single injection of SU5416 (25 mg/kg) followed by 4-weeks exposure to hypoxia and 2-weeks of normoxia. At week 8, animals were randomized to receive either intraperitoneal injection of saline or the MAO-A inhibitor clorgyline 10 mg/kg, followed by 2 mg/kg every 3 days until week 10. Echocardiography and RV catheterization was performed at week 10 and heart and lung tissues were collected for further analysis. Results: Compared to the vehicle group, clorgyline treatment reduced right ventricular (RV) systolic pressure and RV afterload. Moreover, clorgyline improved RV function by reducing RV hypertrophy and stiffness. Further tissue analysis by histology revealed that clorgyline reduced pulmonary vascular remodeling by reducing intima layer thickness. Conclusion: Clorgyline partly reversed RV systolic pressure and RV afterload in established experimental PAH. Together with the observed reduced RV remodeling, MAO-A inhibition may be a promising intervention for PAH. |
| اللغة: | English |
| تدمد: | 0903-1936 |
| DOI: | 10.1183/13993003.congress-2018.PA3072 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4942afaa8953c4d85dc53d88afbcda56 https://research.vumc.nl/en/publications/a31d5f0c-55bc-40f4-96b1-56da222d7a67 |
| Rights: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....4942afaa8953c4d85dc53d88afbcda56 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09031936 |
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| DOI: | 10.1183/13993003.congress-2018.PA3072 |