Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium

Author:

Ivanisenko V. A.1ORCID,Basov N. V.2ORCID,Makarova A. A.3ORCID,Venzel A. S.4ORCID,Rogachev A. D.2ORCID,Demenkov P. S.1ORCID,Ivanisenko T.  V.1ORCID,Kleshchev M. A.3ORCID,Gaisler E. V.2,Moroz G. B.5ORCID,Plesko V. V.5,Sotnikova Y. S.6ORCID,Patrushev Y. V.7ORCID,Lomivorotov V. V.8ORCID,Kolchanov N. A.9ORCID,Pokrovsky A. G.10ORCID

Affiliation:

1. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Kurchatov Genomic Center of ICG SB RAS

2. Novosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences

3. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences

4. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RAS

5. E. Meshalkin National Medical Research Center of the Ministry of Health of Russian Federation

6. Novosibirsk State University; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences

7. Novosibirsk State University; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences

8. E. Meshalkin National Medical Research Center of the Ministry of Health of Russian Federation; Penn State Health Milton S. Hershey Medical Center

9. Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University

10. Novosibirsk State University

Abstract

Postoperative delirium (POD) is considered one of the most severe complications, resulting in impaired cognitive function, extended hospitalization, and higher treatment costs. The challenge of early POD diagnosis becomes particularly significant in cardiac surgery cases, as the incidence of this complication exceeds 50 % in certain patient categories. While it is known that neuroinflammation, neurotransmitter imbalances, disruptions in neuroendocrine regulation, and interneuronal connections contribute significantly to the development of POD, the molecular, genetic mechanisms of POD in cardiac surgery patients, along with potential metabolomic diagnostic markers, remain in adequately understood. In this study, blood plasma was collected from a group of patients over 65 years old after cardiac surgery involving artificial circulation. The collected samples were analyzed for sphingomyelin content and quantity using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS) me thods. The analysis revealed four significantly different sphingomyelin contents in patients with POD compared to those who did not develop POD (control group). Employing gene network reconstruction, we perceived a set of 82 regulatory enzymes affiliated with the genetic coordination of the sphingolipid metabolism pathway. Within this set, 47 are assumed to be regulators of gene expression, governing the transcription of enzymes pivotal to the metabolic cascade. Complementing this, an additional assembly of 35 regulators are considered to be regulators of activity, degradation, and translocation dynamics of enzymes integral to the aforementioned pathway. Analysis of the overrepresentation of diseases with which these regulatory proteins are associated showed that the regulators can be categorized into two groups, associated with cardiovascular pathologies (CVP) and neuropsychiatric diseases (NPD), respectively. The regulators associated with CVP are expectedly related to the effects on myocardial tissue during surgery. It is hypothesized that dysfunction of NPD-associated regulators may specifically account for the development of POD after cardiac surgery. Thus, the identified regulatory genes may provide a basis for planning further experiments, in order to study disorders at the level of expression of these genes, as well as impaired function of proteins encoded by them in patients with POD. The identified significant sphingolipids can be considered as potential markers of POD. 

Publisher

Institute of Cytology and Genetics, SB RAS

Subject

General Biochemistry, Genetics and Molecular Biology,General Agricultural and Biological Sciences

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. FISIOPATOLOGIA E CONDUTA TERAPÊUTICA DO DELIRIUM: UMA REVISÃO BIBLIOGRÁFICA;RECIMA21 - Revista Científica Multidisciplinar - ISSN 2675-6218;2024-06-05

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