1. Blockade of Dopamine D2 Receptors as a Novel Approach to Stimulation of Notch1 + Endothelial Progenitor Cells and Angiogenesis in C57BL/6 Mice with Pulmonary Emphysema Induced by Proteases and Deficiency of α1-Antitrypsin.
- Author
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Skurikhin EG, Krupin VA, Pershina OV, Pan ES, Pakhomova AV, Sandrikina LA, Ermakova NN, Vaizova OE, Zhukova MA, and Dygai AM
- Subjects
- Animals, Endothelial Progenitor Cells metabolism, Endothelial Progenitor Cells pathology, Female, Galactosamine administration & dosage, Gene Expression Regulation, Hepatocytes drug effects, Hepatocytes metabolism, Hepatocytes pathology, Liver drug effects, Liver metabolism, Liver pathology, Lung drug effects, Lung metabolism, Lung pathology, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic drug effects, Pancreatic Elastase administration & dosage, Phosphorylation drug effects, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Pulmonary Emphysema chemically induced, Pulmonary Emphysema genetics, Pulmonary Emphysema metabolism, Receptor, Notch1 agonists, Receptor, Notch1 metabolism, Receptors, Dopamine D2 metabolism, Regeneration drug effects, Vascular Endothelial Growth Factor Receptor-2 genetics, Vascular Endothelial Growth Factor Receptor-2 metabolism, alpha 1-Antitrypsin genetics, alpha 1-Antitrypsin metabolism, alpha 1-Antitrypsin Deficiency enzymology, alpha 1-Antitrypsin Deficiency genetics, alpha 1-Antitrypsin Deficiency pathology, Dopamine Antagonists pharmacology, Endothelial Progenitor Cells drug effects, Pulmonary Emphysema drug therapy, Receptor, Notch1 genetics, Receptors, Dopamine D2 genetics, Spiperone pharmacology, alpha 1-Antitrypsin Deficiency drug therapy
- Abstract
We studied the effects of spiperone, a selective blocker of dopamine D2 receptors, on the model of pulmonary emphysema provoked by administration of elastase and D-galactosamine hydrochloride to female C57BL/6 mice and characterized by activation of proteases in the lungs and systemic deficiency of its inhibitor α1-antitrypsin. In this model, spiperone prevented the development of inflammatory reaction and reduced the area of emphysematous expanded alveolar tissue. The expression of angiogenic marker CD31 in the lungs increased under these conditions. Regeneration of the damaged microvascular bed under the action of spiperone resulted from recruiting of Notch1
+ endothelial progenitor cells (CD45- CD31+ CD34+ ) into the lungs and blockade of the inhibitory effect of dopamine on phosphorylation of VEGF-2 receptors in endothelial cells of different maturity. In addition, spiperone produced a protective effect on hepatocytes and restored the production and secretion of α1-antitrypsin by these cells.- Published
- 2020
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