Koo2013 - Integrated shear stress induced NO production model

Model Identifier
BIOMD0000000468
Short description
Andrew Koo, David Nordsletten, Renato Umeton, Beracah Yankama, Shiva Ayyadurai, Guillermo García-Cardeña & C. Forbes Dewey. In silico modeling of shear-stress-induced nitric oxide production in endothelial cells through systems biology. Biophysical Journal 104, 10 (2013).

Nitric oxide (NO) produced by vascular endothelial cells is a potent vasodilator and an antiinflammatory mediator. Regulating production of endothelial-derived NO is a complex undertaking, involving multiple signaling and genetic pathways that are activated by diverse humoral and biomechanical stimuli. To gain a thorough understanding of the rich diversity of responses observed experimentally, it is necessary to account for an ensemble of these pathways acting simultaneously. In this article, we have assembled four quantitative molecular pathways previously proposed for shear-stress-induced NO production. In these pathways, endothelial NO synthase is activated 1), via calcium release, 2), via phosphorylation reactions, and 3), via enhanced protein expression. To these activation pathways, we have added a fourth, a pathway describing actual NO production from endothelial NO synthase and its various protein partners. These pathways were combined and simulated using CytoSolve, a computational environment for combining independent pathway calculations. The integrated model is able to describe the experimentally observed change in NO production with time after the application of fluid shear stress. This model can also be used to predict the specific effects on the system after interventional pharmacological or genetic changes. Importantly, this model reflects the up-to-date understanding of the NO system, providing a platform upon which information can be aggregated in an additive way.
Format
SBML (L2V4)
Related Publication
  • In silico modeling of shear-stress-induced nitric oxide production in endothelial cells through systems biology. Click here to expand
  • Andrew Koo, David Nordsletten, Renato Umeton, Beracah Yankama, Shiva Ayyadurai, Guillermo García-Cardeña, C Forbes Dewey
  • Biophysical journal , 5/ 2013 , Volume 104 , Issue 10 , pages: 2295-2306 , PubMed ID: 23708369
  • Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Nitric oxide (NO) produced by vascular endothelial cells is a potent vasodilator and an antiinflammatory mediator. Regulating production of endothelial-derived NO is a complex undertaking, involving multiple signaling and genetic pathways that are activated by diverse humoral and biomechanical stimuli. To gain a thorough understanding of the rich diversity of responses observed experimentally, it is necessary to account for an ensemble of these pathways acting simultaneously. In this article, we have assembled four quantitative molecular pathways previously proposed for shear-stress-induced NO production. In these pathways, endothelial NO synthase is activated 1), via calcium release, 2), via phosphorylation reactions, and 3), via enhanced protein expression. To these activation pathways, we have added a fourth, a pathway describing actual NO production from endothelial NO synthase and its various protein partners. These pathways were combined and simulated using CytoSolve, a computational environment for combining independent pathway calculations. The integrated model is able to describe the experimentally observed change in NO production with time after the application of fluid shear stress. This model can also be used to predict the specific effects on the system after interventional pharmacological or genetic changes. Importantly, this model reflects the up-to-date understanding of the NO system, providing a platform upon which information can be aggregated in an additive way.
Contributors
Submitter of the first revision: Vijayalakshmi Chelliah
Submitter of this revision: Lucian Smith
Curator: Lucian Smith
Modellers: administrator, Vijayalakshmi Chelliah

Metadata information

is (2 statements)
BioModels Database BIOMD0000000468
BioModels Database MODEL1308190000

isDerivedFrom (4 statements)
BioModels Database BIOMD0000000464
BioModels Database BIOMD0000000465
BioModels Database BIOMD0000000466
BioModels Database BIOMD0000000467

isDescribedBy (1 statement)
PubMed 23708369

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (2 statements)
hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model

Connected external resources