Journal
ANNALS OF BIOMEDICAL ENGINEERING
Volume 38, Issue 2, Pages 291-307Publisher
SPRINGER
DOI: 10.1007/s10439-009-9822-y
Keywords
Atherosclerosis; Bone Morphogenic Protein 4 (BMP4); Biochemical Systems Theory (BST); Inflammation; Mechanosensing; Monocyte adhesion; NADPH oxidase; Shear stress
Categories
Funding
- University Systems of Georgia
- Georgia Research Alliance
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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 p47(phox)-dependent NADPH oxidases in endothelial inflammation.
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