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.
  • Koo A, Nordsletten D, Umeton R, Yankama B, Ayyadurai S, García-Cardeña G, Dewey CF Jr
  • Biophysical journal , 5/ 2013 , Volume 104 , 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
Modellers: Andrew Koo

Metadata information

BioModels Database MODEL1302180006
BioModels Database BIOMD0000000467
PubMed 23708369
Taxonomy Homo sapiens

Curation status

Original model(s)


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Model files

BIOMD0000000467_url.xml SBML L2V4 representation of Koo2013 - Shear stress induced NO production - Model 4 141.29 KB Preview | Download

Additional files

BIOMD0000000467-biopax2.owl Auto-generated BioPAX (Level 2) 40.65 KB Preview | Download
BIOMD0000000467-biopax3.owl Auto-generated BioPAX (Level 3) 65.79 KB Preview | Download
BIOMD0000000467.m Auto-generated Octave file 8.52 KB Preview | Download
BIOMD0000000467.pdf Auto-generated PDF file 261.82 KB Preview | Download
BIOMD0000000467.png Auto-generated Reaction graph (PNG) 845.48 KB Preview | Download
BIOMD0000000467.sci Auto-generated Scilab file 205.00 Bytes Preview | Download
BIOMD0000000467.svg Auto-generated Reaction graph (SVG) 87.98 KB Preview | Download
BIOMD0000000467.vcml Auto-generated VCML file 62.80 KB Preview | Download
BIOMD0000000467.xpp Auto-generated XPP file 5.55 KB Preview | Download
BIOMD0000000467_urn.xml Auto-generated SBML file with URNs 140.58 KB Preview | Download

  • 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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: Variable used inside SBML models

Reactions Rate Parameters
s45 => s117 + s47; s45 kD*s45 kD = 9.45E-5 inv_sec
s61 => s50 + s57; s61 k7*s61 k7 = 1.5 inv_sec
s51 + s47 => s45; s47, s51 k4*s47*s51 k4 = 0.015 inv_sec_sub
s52 => s48; s3, s3, s52, s48 k1*s3*s52-k1r*s48 k1 = 0.004 inv_sec_sub; k1r = 10.3 inv_sec
s58 => s60; s27, s58, s27, s60 k10*s58*s27/(s58+Km10)-V10r*s60/(s60+Km10r) V10r = 4.0 sub_sec; Km10r = 20.0 substance; Km10 = 5.0 substance; k10 = 0.1 inv_sec
s66 => s51 + s57; s66 k7*s66 k7 = 1.5 inv_sec
s50 => s117 + s48; s50 kD*s50 kD = 9.45E-5 inv_sec
s60 => s57 + s47; s60 kD*s60 kD = 9.45E-5 inv_sec
s48 + s51 => s50; s51, s48, s50 k3*s51*s48-k3r*s50 k3r = 1.5 inv_sec; k3 = 1.5E-4 inv_sec_sub
s45 + s57 => s58; s45, s57 k6*s45*s57 k6 = 0.002 inv_sec_sub
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).