Dataset Information

Vascular Adaptation: Pattern Formation and Cross Validation between an Agent Based Model and a Dynamical System.

ABSTRACT: Myocardial infarction is the global leading cause of mortality (Go et al., 2014). Coronary artery occlusion is its main etiology and it is commonly treated by Coronary Artery Bypass Graft (CABG) surgery (Wilson et al, 2007). The long-term outcome remains unsatisfactory (Benedetto, 2016) as the graft faces the phenomenon of restenosis during the post-surgery, which consists of re-occlusion of the lumen and usually requires secondary intervention even within one year after the initial surgery (Harskamp, 2013). In this work, we propose an extensive study of the restenosis phenomenon by implementing two mathematical models previously developed by our group: a heuristic Dynamical System (DS) (Garbey and Berceli, 2013), and a stochastic Agent Based Model (ABM) (Garbey et al., 2015). With an extensive use of the ABM, we retrieved the pattern formations of the cellular events that mainly lead the restenosis, especially focusing on mitosis in intima, caused by alteration in shear stress, and mitosis in media, fostered by alteration in wall tension. A deep understanding of the elements at the base of the restenosis is indeed crucial in order to improve the final outcome of vein graft bypass. We also turned the ABM closer to the physiological reality by abating its original assumption of circumferential symmetry. This allowed us to finely replicate the trigger event of the restenosis, i.e. the loss of the endothelium in the early stage of the post-surgical follow up (Roubos et al., 1995) and to simulate the encroachment of the lumen in a fashion aligned with histological evidences (Owens et al., 2015). Finally, we cross-validated the two models by creating an accurate matching procedure. In this way we added the degree of accuracy given by the ABM to a simplified model (DS) that can serve as powerful predictive tool for the clinic.

SUBMITTER: Garbey M

PROVIDER: S-EPMC5572567 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Vascular Adaptation: Pattern Formation and Cross Validation between an Agent Based Model and a Dynamical System.

Garbey Marc M Casarin Stefano S Berceli Scott A SA

Journal of theoretical biology 20170621

Myocardial infarction is the global leading cause of mortality (Go et al., 2014). Coronary artery occlusion is its main etiology and it is commonly treated by Coronary Artery Bypass Graft (CABG) surgery (Wilson et al, 2007). The long-term outcome remains unsatisfactory (Benedetto, 2016) as the graft faces the phenomenon of restenosis during the post-surgery, which consists of re-occlusion of the lumen and usually requires secondary intervention even within one year after the initial surgery (Har ...[more]

PMID: 28645858

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Project description:The development of multicellular organisms involves cells to decide their fate upon the action of biochemical signals. This decision is often spatiotemporally coordinated such that a spatial pattern arises. The dynamics that drive pattern formation usually involve genetic nonlinear interactions and positive feedback loops. These complex dynamics may enable multiple stable patterns for the same conditions. Under these circumstances, pattern formation in a developing tissue involves a selection process: why is a certain pattern formed and not another stable one? Herein we computationally address this issue in the context of the Notch signaling pathway. We characterize a dynamical mechanism for developmental selection of a specific pattern through spatiotemporal changes of the control parameters of the dynamics, in contrast to commonly studied situations in which initial conditions and noise determine which pattern is selected among multiple stable ones. This mechanism can be understood as a path along the parameter space driven by a sequence of biochemical signals. We characterize the selection process for three different scenarios of this dynamical mechanism that can take place during development: the signal either 1) acts in all the cells at the same time, 2) acts only within a cluster of cells, or 3) propagates along the tissue. We found that key elements for pattern selection are the destabilization of the initial pattern, the subsequent exploration of other patterns determined by the spatiotemporal symmetry of the parameter changes, and the speeds of the path compared to the timescales of the pattern formation process itself. Each scenario enables the selection of different types of patterns and creates these elements in distinct ways, resulting in different features. Our approach extends the concept of selection involved in cellular decision-making, usually applied to cell-autonomous decisions, to systems that collectively make decisions through cell-to-cell interactions.

Dataset Information

Vascular Adaptation: Pattern Formation and Cross Validation between an Agent Based Model and a Dynamical System.

Publications

Vascular Adaptation: Pattern Formation and Cross Validation between an Agent Based Model and a Dynamical System.

Similar Datasets

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