Koo2013 - Shear stress induced NO production - Model 4

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  • 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.
Submitter of the first revision: Andrew Koo
Submitter of this revision: Andrew Koo
Modeller: Andrew Koo

Metadata information

is (2 statements)
BioModels Database BIOMD0000000467
BioModels Database MODEL1302180006

isDescribedBy (1 statement)
PubMed 23708369

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (3 statements)

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  • Model originally submitted by : Andrew Koo
  • Submitted: Feb 18, 2013 8:30:04 PM
  • Last Modified: Apr 7, 2014 4:05:10 AM
  • Version: 2 public model Download this version
    • Submitted on: Apr 7, 2014 4:05:10 AM
    • Submitted by: Andrew Koo
    • With comment: Current version of Koo2013 - Shear stress induced NO production - Model 4
  • Version: 1 public model Download this version
    • Submitted on: Feb 18, 2013 8:30:04 PM
    • Submitted by: Andrew Koo
    • With comment: Original import of BIOMD0000000467.xml.origin

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Curator's comment:
(added: 19 Aug 2013, 14:10:20, updated: 19 Aug 2013, 14:10:20)
The paper describes four sub-models and an integrated version of the four sub-models. This model corresponds to Model 4 - Shear stress induced NO production. There is no Figure corresponding to this sub-model in the paper. Refer to the integrated model (MODEL1308190000).