EURO 2024 Copenhagen
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4013. Identifying Key Therapeutic Targets for Treating Hyperglycemia-Induced Atherosclerosis Using a Petri Net-Based Model

Invited abstract in session TC-20: Integrative Approaches in Health and Disease: From Molecular Structures to Clinical Outcomes, stream Computational Biology, Bioinformatics and Medicine.

Tuesday, 12:30-14:00
Room: 45 (building: 116)

Authors (first author is the speaker)

1. Agnieszka Rybarczyk
Institute of Computing Science, Poznan University of Technology
2. Dorota Formanowicz
Poznan University of Medical Sciences
3. Piotr Formanowicz
Institute of Computing Science, Poznan University of Technology

Abstract

Persistent high glucose levels, a hallmark of diabetes mellitus (DM), lead to widespread cellular damage. Atherosclerosis, occurring alongside glucose metabolism disturbances, significantly complicates the condition and accelerates in DM, making it critical to slow its progression. Identifying intervention targets within the complex network of molecules and processes, without disrupting essential functions, is challenging. Here, computational testing, like in silico analysis, becomes crucial for identifying potential therapeutic targets effectively. In our study, we used a Petri net model to identify key network nodes whose blockade could impede atherosclerosis in hyperglycemia. Our findings suggest that inhibiting isoforms of protein kinase C in diabetic patients could help slow the progression of atherosclerosis. Additionally, we observed that inhibiting aldose reductase could decelerate atherosclerosis advancement and reduce PKC expression in DM. Targeting oxidative stress by inhibiting the AGE-RAGE axis emerges as a promising therapeutic strategy for managing hyperglycemia-induced atherosclerosis. While blocking NADPH oxidase, the primary enzyme responsible for generating reactive oxygen species (ROS) in blood vessels, only marginally impeded atherosclerosis development, it effectively halted the increased production of mitochondrial ROS associated with mitochondrial dysfunction. These findings lay the groundwork for more in-depth studies.

Keywords

Status: accepted

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