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Gender Differences in the Pharmacological Actions of Pegylated Glucagon-Like Peptide-1 on Endothelial Progenitor Cells and Angiogenic Precursor Cells in a Combination of Metabolic Disorders and Lung Emphysema

1
Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, 634028 Tomsk, Russia
2
Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights campus, Reading RG6 6AP, UK
3
Branch Federal State Unitary Enterprise “Scientific and Production Association for Immunological Preparations “Microgen” of Ministry of Health of the Russian Federation “SIC “Virion” in Tomsk, 634040 Tomsk, Russia
4
Department of Pharmacology, Siberian State Medical University, 634050 Tomsk, Russia
5
Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5414; https://doi.org/10.3390/ijms20215414
Received: 23 September 2019 / Revised: 20 October 2019 / Accepted: 27 October 2019 / Published: 30 October 2019
(This article belongs to the Special Issue Peptides for Health Benefits 2019)
In clinical practice, the metabolic syndrome (MetS) is often associated with chronic obstructive pulmonary disease (COPD). Although gender differences in MetS are well documented, little is known about sex-specific differences in the pathogenesis of COPD, especially when combined with MetS. Consequently, it is not clear whether the same treatment regime has comparable efficacy in men and women diagnosed with MetS and COPD. In the present study, using sodium glutamate, lipopolysaccharide, and cigarette smoke extract, we simulated lipid metabolism disorders, obesity, hyperglycemia, and pulmonary emphysema (comorbidity) in male and female C57BL/6 mice. We assessed the gender-specific impact of lipid metabolism disorders and pulmonary emphysema on angiogenic precursor cells (endothelial progenitor cells (EPC), pericytes, vascular smooth muscle cells, cells of the lumen of the nascent vessel), as well as the biological effects of pegylated glucagon-like peptide 1 (pegGLP-1) in this experimental paradigm. Simulation of MetS/COPD comorbidity caused an accumulation of EPC (CD45CD31+CD34+), pericytes, and vascular smooth muscle cells in the lungs of female mice. In contrast, the number of cells involved in the angiogenesis decreased in the lungs of male animals. PegGLP-1 had a positive effect on lipids and area under the curve (AUC), obesity, and prevented the development of pulmonary emphysema. The severity of these effects was stronger in males than in females. Furthermore, PegGLP-1 stimulated regeneration of pulmonary endothelium. At the same time, PegGLP-1 administration caused a mobilization of EPC (CD45CD31+CD34+) into the bloodstream in females and migration of precursors of angiogenesis and vascular smooth muscle cells to the lungs in male animals. Gender differences in stimulatory action of pegGLP-1 on CD31+ endothelial lung cells in vitro were not observed. Based on these findings, we postulated that the cellular mechanism of in vivo regeneration of lung epithelium was at least partly gender-specific. Thus, we concluded that a pegGLP-1-based treatment regime for metabolic disorder and COPD should be further developed primarily for male patients. View Full-Text
Keywords: gender differences; dyslipidemia; obesity; hyperglycemia; pulmonary emphysema; endothelial progenitor cells; angiogenic precursor cells; pegylated glucagon-like peptide 1; and endothelial regeneration gender differences; dyslipidemia; obesity; hyperglycemia; pulmonary emphysema; endothelial progenitor cells; angiogenic precursor cells; pegylated glucagon-like peptide 1; and endothelial regeneration
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Pershina, O.V.; Pakhomova, A.V.; Widera, D.; Ermakova, N.N.; Epanchintsev, A.A.; Pan, E.S.; Krupin, V.A.; Vaizova, O.E.; Putrova, O.D.; Sandrikina, L.A.; Kurochkina, I.V.; Morozov, S.G.; Kubatiev, A.A.; Dygai, A.M.; Skurikhin, E.G. Gender Differences in the Pharmacological Actions of Pegylated Glucagon-Like Peptide-1 on Endothelial Progenitor Cells and Angiogenic Precursor Cells in a Combination of Metabolic Disorders and Lung Emphysema. Int. J. Mol. Sci. 2019, 20, 5414.

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