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Author Notes:

Address correspondence to Eberhard O. Voit, Integrative Bio-Systems Institute, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA 30332, USA. eberhard.voit@bme.gatech.edu

Subjects:

Research Funding:

The work was supported in part by grants from the University Systems of Georgia and the Georgia Research Alliance.

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Engineering
  • ENGINEERING, BIOMEDICAL
  • Atherosclerosis
  • Bone Morphogenic Protein 4 (BMP4)
  • Biochemical Systems Theory (BST)
  • Inflammation
  • Mechanosensing
  • Monocyte adhesion
  • NADPH oxidase
  • Shear stress
  • LAMINAR SHEAR-STRESS
  • SMOOTH-MUSCLE-CELLS
  • NADPH OXIDASE ACTIVATION
  • REACTIVE OXYGEN
  • HYDROGEN-PEROXIDE
  • NAD(P)H OXIDASES
  • GENE-EXPRESSION
  • ANGIOTENSIN-II
  • CARDIOVASCULAR-SYSTEM
  • SUPEROXIDE-DISMUTASE

Systems Analysis of the Role of Bone Morphogenic Protein 4 in Endothelial Inflammation

Tools:

Journal Title:

Annals of Biomedical Engineering

Volume:

Volume 38, Number 2

Publisher:

, Pages 291-307

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Shear stress is an important factor in the onset and progression of atherosclerosis. High and unidirectional laminar stress is seen as protective, while low and oscillatory shear stress is considered pro-inflammatory and pro-atherogenic. The mechanosensitive response of endothelial cells is governed by a complex system of genes, proteins, and signals that operate at distinctly different time scales. We propose a dynamic mathematical model that quantitatively describes this mechanosensing system and permits novel insights into its functioning. The model, the first of its kind, is constructed within the guidelines of Biochemical Systems Theory and accounts for different time scales by means of approximated delays. Parameter values are obtained directly from biochemical observations in an ad hoc fashion. The model reflects most documented observations well and leads to a number of predictions and novel hypotheses. In particular, it demonstrates the crucial role of Bone Morphogenic Protein 4 and p47phox-dependent NADPH oxidases in endothelial inflammation.

Copyright information:

Copyright © 2009, Biomedical Engineering Society.

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