The Role of Macrophage Dynamics in Atherosclerosis Analyzed Using a Petri Net-Based Model

Abstract

Atherosclerosis, a chronic inflammatory and oxidative stress-mediated disease impacting the arterial system, stands as a primary cause of morbidity and mortality worldwide. The complexity of this disease, driven by numerous factors, requires a thorough investigation of its underlying mechanisms. In our study, we explore the complex interplay between cholesterol homeostasis, macrophage dynamics, and atherosclerosis development using a Petri net-based model anchored in credible, peer-reviewed biological and medical research. Our findings underscore the significant role of macrophage colony-stimulating factor (M-CSF) inhibition in reducing atherosclerotic plaque formation by modulating inflammatory responses and lipid accumulation. Furthermore, our model highlights the therapeutic potential of targeting the C-X-C motif ligand 12 (CXCL12)/ C-X-C motif chemokine receptor type 4 (CXCR4) pathway to hinder hematopoietic stem and progenitor cells’ (HSPCs’) mobilization and plaque development. Based on the results obtained, which are in agreement with current studies, additional strategies are also proposed, such as decreasing M1 macrophage polarization for therapeutic gains, opening the door to future research and novel treatment approaches.

Keywords

• macrophage
• atherosclerosis
• mathematical modeling
• Petri nets
• knockout analysis