Affiliation:
1. Federal Research Center “Informatics and Management”, Russian Academy of Sciences
2. Orekhovich Research Institute of Biomedical Chemistry, Center for Collective Use “Human Proteome”
3. Pirogov Russian National Research Medical University
4. Russian Medical Academy of Continuing Professional Education
Abstract
Objective: identification of peptides in the composition of Laennec®, which can inhibit the development of endotheliopathy (endothelial dysfunction).Material and methods. Hybrid mass spectrometry followed by data analysis based on topological recognition theory was performed. The analysis of the peptide composition of Laennec® included four stages: purification of the drug, chromatographic separation of peptides, determination of the multidimensional mass spectrum of the peptide fraction, and de novo sequencing of the isolated peptides.Results. The preparation contains peptides-inhibitors of specific target proteins (PRKCZ, PKB, PKD1, MAPK14, IKKB, PDPK1) involved in the activation of the pro-inflammatory transcription factor NF-κB. Inhibition of CDK5 and SHC1 kinases helps to reduce endothelial cell apoptosis. The peptides of the drug also block enzymes involved in the synthesis and maturation of the tumor necrosis factor alpha (MAPKAPK2/3, ADAM17).Conclusion. In the composition of Laennec®, peptides have been found that contribute to a complex pathogenetic action against endotheliopathy. Endothelial regeneration is especially important in the rehabilitation of patients who have recovered from COVID-19.
Subject
Public Health, Environmental and Occupational Health,Health Policy,Pharmacology
Reference53 articles.
1. Puzik S.G. Endothelial dysfunction in the pathogenesis of arterial hypertension and the progression of atherosclerosis. Semeynaya meditsina / Family Medicine. 2018; 2: 69–74 (in Russ.).
2. Chuchalin A.G. A role of nitric oxide for the modern clinical practice: a scientific report at the 5th Pan-Russian Congress on pulmonary hypertension, December 13, 2017. Pulmonologiya. 2018; 28 (4): 503–11 (in Russ.). https://doi.org/10.18093/0869-0189-2018-28-4-503-511.
3. Panina I.Y., Petrichshtev N.N., Smirnov A.V., et al. Arterial hypertension and endothelial dysfunction in chronic kidney diseases. Arterial’naya gipertenziya / Arterial Hypertension. 2006; 12 (4): 352–7 (in Russ.). https://doi.org/10.18705/1607-419X-2006-12-4-352-357.
4. Sholkava M.V., Dotsenko E.A. Endothelial dysfunction in chronic obstructive pulmonary diseases. Emergency Cardiology and Cardiovascular Risks. 2019; 3 (1): 539–45 (in Russ.).
5. Liu C., Jiang Z.C., Shao C.X., Zhang H.G., et al. Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study. Zhonghua Gan Zang Bing Za Zhi. 2020; 28 (2): 148–52 (in Chinese). https://doi.org/10.3760/cma.j.issn.1007-3418.2020.02.003.