Abstract
The functioning of both normal and pathological tissues depends on an adequate supply of oxygen through the blood vessels. A process called angiogenesis, in which new endothelial cells and smooth muscles interact with each other, forming new blood vessels either from the existing ones or from a primary vascular plexus, is particularly important and interesting, due to new therapeutic possibilities it offers. This is a multi-step and very complex process, so an accurate understanding of the underlying mechanisms is a significant task, especially in recent years, with the constantly increasing amount of new data that must be taken into account. A systems approach is necessary for these studies because it is not sufficient to analyze the properties of the building blocks separately and an analysis of the whole network of interactions is essential. This approach is based on building a mathematical model of the system, while the model is expressed in the formal language of a mathematical theory. Recently, the theory of Petri nets was shown to be especially promising for the modeling and analysis of biological phenomena. This analysis, based mainly on t-invariants, has led to a particularly important finding that a direct link (close connection) exist between transforming growth factor β1 (TGF-β1), endothelial nitric oxide synthase (eNOS), nitric oxide (NO), and hypoxia-inducible factor 1, the molecules that play a crucial roles during angiogenesis. We have shown that TGF-β1 may participate in the inhibition of angiogenesis through the upregulation of eNOS expression, which is responsible for catalyzing NO production. The results obtained in the previous studies, concerning the effects of NO on angiogenesis, have not been conclusive, and therefore, our study may contribute to a better understanding of this phenomenon.
Highlights
The rapidly increasing amount of data concerning the molecular aspects of biological processes led to a conclusion that living organisms represent complex systems, composed of basic building blocks connected by a dense interaction network
hypoxia-inducible factor 1 (HIF-1) consists of two subunits, α and β, and HIF family consists of three α and three β isoforms [16], but we have considered the importance of HIF-1 α and β isoforms only, and the impact of HIF-2 α isoform on erythropoiesis in our model
They reside in places and flow from one place to another through transitions
Summary
The rapidly increasing amount of data concerning the molecular aspects of biological processes led to a conclusion that living organisms represent complex systems, composed of basic building blocks connected by a dense interaction network.
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