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Article

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Title

Key Therapeutic Targets to Treat Hyperglycemia-Induced Atherosclerosis Analyzed Using a Petri Net-Based Model

Authors

[ 1 ] Instytut Informatyki, Wydział Informatyki i Telekomunikacji, Politechnika Poznańska | [ P ] employee

Scientific discipline (Law 2.0)

[2.3] Information and communication technology

Year of publication

2023

Published in

Metabolites

Journal year: 2023 | Journal volume: vol. 13 | Journal number: iss. 12

Article type

scientific article

Publication language

english

Keywords
EN
  • diabetes mellitus
  • atherosclerosis
  • modeling
  • Petri nets
  • knockout analysis
Abstract

EN Chronic superphysiological glucose concentration is a hallmark of diabetes mellitus (DM) and a cause of damage to many types of cells. Atherosclerosis coexists with glucose metabolism disturbances, constituting a significant problem and exacerbating its complications. Atherosclerosis in DM is accelerated, so it is vital to slow its progression. However, from the complex network of interdependencies, molecules, and processes involved, choosing which ones should be inhibited without blocking the pathways crucial for the organism’s functioning is challenging. To conduct this type of analysis, in silicotesting comes in handy. In our study, to identify sites in the network that need to be blocked to have an inhibitory effect on atherosclerosis in hyperglycemia, which is toxic for the human organism, we created a model using Petri net theory and performed analyses. We have found that blocking isoforms of protein kinase C (PKC)—PKC𝛽 and PKC𝛾—in diabetic patients can contribute to the inhibition of atherosclerosis progression. In addition, we have discovered that aldose reductase inhibition can slow down atherosclerosis progression, and this has been shown to reduce PKC (𝛽 and 𝛾) expression in DM. It has also been observed that diminishing oxidative stress through the inhibitory effect on the AGE-RAGE axis may be a promising therapeutic approach in treating hyperglycemia-induced atherosclerosis. Moreover, the blockade of NADPH oxidase, the key enzyme responsible for the formation of reactive oxygen species (ROS) in blood vessels, only moderately slowed down atherosclerosis development. However, unlike aldose reductase blockade, or direct PKC (𝛽 and 𝛾), the increased production of mitochondrial ROS associated with mitochondrial dysfunction effectively stopped after NADPH oxidase blockade. The results obtained may constitute the basis for further in-depth research.

Date of online publication

08.12.2023

Pages (from - to)

1191-1 - 1191-28

DOI

10.3390/metabo13121191

URL

https://www.mdpi.com/2218-1989/13/12/1191

Comments

Article Number: 1191

License type

CC BY (attribution alone)

Open Access Mode

open journal

Open Access Text Version

final published version

Date of Open Access to the publication

at the time of publication

Ministry points / journal

100

Impact Factor

3,4

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