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.
Andrew Koo

Metadata information

BioModels Database MODEL1302180006
BioModels Database BIOMD0000000467
PubMed 23708369
Taxonomy Homo sapiens

Curation status

Original model(s)

Name Description Size Actions

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

  • Model originally submitted by : Andrew Koo
  • Submitted: 18-Feb-2013 20:30:04
  • Last Modified: 07-Apr-2014 04:05:10
  • Version: 2 public model Download this version
    • Submitted on: 07-Apr-2014 04:05:10
    • 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: 18-Feb-2013 20:30:04
    • Submitted by: Andrew Koo
    • With comment: Original import of BIOMD0000000467.xml.origin

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

: Variable used inside SBML models

Reactions Rate Parameters
s48 => s47; s3, s3, s48, s47 k2*s3*s48-k2r*s47 k2r = 1152.0 inv_sec; k2 = 0.08 inv_sec_sub
s62 => s65 + s48; s62, s65, s48 k3r*s62-k3*s65*s48 k3r = 1.5 inv_sec; k3 = 1.5E-4 inv_sec_sub
s50 => s117 + s48; s50 kD*s50 kD = 9.45E-5 inv_sec
s62 => s57 + s48; s62 kD*s62 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
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
s66 => s51 + s57; s66 k7*s66 k7 = 1.5 inv_sec
s52 => s48; s3, s3, s52, s48 k1*s3*s52-k1r*s48 k1 = 0.004 inv_sec_sub; k1r = 10.3 inv_sec
s61 => s62; s27, s61, s27, s62 k10*s61*s27/(s61+Km10)-V10r*s62/(s62+Km10r) V10r = 4.0 sub_sec; Km10r = 20.0 substance; Km10 = 5.0 substance; k10 = 0.1 inv_sec
s61 => s57 + s48; s61 kD*s61 kD = 9.45E-5 inv_sec
s60 => s62; s3, s60, s3, s62 k5*s60-k2*s3*s62 k5 = 115.2 inv_sec; k2 = 0.08 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).