252 - Causal biological network model of endothelial dysfunction as a predictor of arterial aging (ID 470)
Abstract
Background and Aims
Aging, as well as smoking, is associated with progressive changes in arterial structure and function. In arterial trees, arterial aging is characterized by endothelial dysfunction (ED) and arterial remodeling, indicating a decline in arterial elasticity and compliance and increase in arterial stiffness. Oxidative stress (NO–antioxidant imbalance), inflammation, and cell senescence represent major mechanisms involved in ED and vascular system degeneration and sclerosis. This study aimed to build a causal biological network model as a diagnostic tool for forecasting cardiovascular aging through transcriptomics dysregulations.
Methods
Biological Expression Language (BEL) statements, representing the ED network model, were compiled by using the OpenBEL framework 3.0.0. Cytoscape.
Results
In the ED network model, vascular contraction and vasodilation were closely related to arterial aging via adiponectin and NO activity. Adiponectin is a putative biomarker for ED, and its effect on endothelial function emerged through its interaction with endothelial nitric oxide synthase (eNOS). Our model also contains Sirt1, a longevity regulator, as a crucial NAD+-dependent deacetylase involved in antioxidative pathways related to NOx, superoxide dismutase, and eNOS modulation.
Conclusions
We developed a causal biological network model that could be used as a diagnostic tool for predicting cardiovascular aging through transcriptomics dysregulations. In the context of interventional studies, the ED network model could be used to analyze the impact of smoking or reduced-risk products on cardiovascular aging by using transcriptomics data. This network model will be available on the CBN (http://causalbionet.com/) platform and can, thereby, serve the wider community for studying the impact of interventions.
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