Spiperone stimulates regeneration in pulmonary endothelium damaged by cigarette smoke and lipopolysaccharide
| Autor: | Evgenii Skurikhin, Olga Pershina, Mariia Zhukova, Darius Widera, Edgar Pan, Angelina Pakhomova, Vyacheslav Krupin, Natalia Ermakova, Victoria Skurikhina, Lubov Sandrikina, Sergey Morozov, Aslan Kubatiev, Alexander Dygai |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Notch1 General Medicine International Journal of Chronic Obstructive Pulmonary Disease respiratory tract diseases Cigarette Smoking Mice Inbred C57BL Mice Pulmonary Disease Chronic Obstructive endothelial regeneration Pulmonary Emphysema Spiperone cardiovascular system Animals Humans Regeneration Female Endothelium Lung Original Research VEGF2 (CD309) Endothelial Progenitor Cells |
| Zdroj: | International Journal of Chronic Obstructive Pulmonary Disease |
| ISSN: | 1178-2005 |
| Popis: | Evgenii Skurikhin,1 Olga Pershina,1 Mariia Zhukova,1 Darius Widera,2 Edgar Pan,1 Angelina Pakhomova,1 Vyacheslav Krupin,1 Natalia Ermakova,1 Victoria Skurikhina,3 Lubov Sandrikina,1 Sergey Morozov,4 Aslan Kubatiev,4 Alexander Dygai1,4 1Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Tomsk, Russia; 2Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights Campus, Reading, RG6 6AP, UK; 3Siberian State Medical University, Tomsk, Russia; 4Institute of General Pathology and Pathophysiology, Moscow, RussiaCorrespondence: Evgenii SkurikhinLaboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, 634028, 3, Lenin Street, Tomsk, RussiaTel/Fax +7-3822-418-375Email eskurihin@inbox.ruBackground: Endothelial dysfunction and destruction of the pulmonary microcirculation are important pathogenic factors in chronic obstructive pulmonary disease (COPD). In COPD, bronchial obstruction is associated with endothelial dysfunction. Thus, new pharmacological treatment options aimed at restoring the pulmonary endothelium represent a clinical need in COPD therapy. Notch1 has been shown to protect cells against apoptosis, inflammation, and oxidative stress caused by cigarette smoke extract (CSE). Therefore, drug which effect on Notch1 may be a potential therapeutic target for COPD in the future.Methods: In this study, we assessed the potential of spiperone to mediate regeneration of pulmonary endothelium in model of pulmonary emphysema induced by a CSE and lipopolysaccharide (LPS) in female C57BL/6 mice.Results: Spiperone increased the number of capillaries as well as the expression of the CD31 in the alveolar tissue compared to the controls. Moreover, application of spiperone prevented alveolar wall destruction (DI), and reduced the area of emphysema. Lastly, we demonstrated that spiperone positively influenced mobilization and migration of endothelial progenitor cells (EPC, CD45âCD34+CD31+), CD309+-endothelial cells, and angiogenesis precursors (CD45âCD117+CD309+) into the lung. Spiperone administration significantly reduced the number Notch1 positive CD309+-endothelial cells and Notch1+ EPCs.Conclusion: Overall, our results suggest that spiperone mediates endothelial regeneration in an animal model of COPD. Thus, it could represent a novel therapeutic approach for treatment of emphysema associated with COPD.Keywords: pulmonary emphysema, endothelial progenitor cells, VEGF2 (CD309), spiperone, Notch1, endothelial regeneration |
| Databáze: | OpenAIRE |
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