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A multiscale computational model of microcirculatory vasoreactivity: Linking subcellular events to macroscale responses in health and disease
Author(s) -
Kapela Adam,
Gadkari Tushar,
Tsoukias Nikolaos M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.627.12
Subject(s) - intracellular , neuroscience , multicellular organism , vascular tone , biology , microbiology and biotechnology , chemistry , cell , vasodilation , endocrinology , biochemistry
Microcirculatory tone is regulated by an elaborate system of intracellular and intercellular signaling pathways. We developed an integrated mathematical model to elucidate how this regulation emerges from the nonlinear interaction of individual cellular components and mechanisms. Detailed descriptions of calcium dynamics and membrane electrophysiology in isolated endothelial and smooth muscle cells are validated against subcellular‐ and cellular‐level data. A multicellular vessel segment is formulated by integrating individual cells and accounting for intercellular communication. The passive and active biomechanical properties of the vessel are accounted in simulating diameter changes. The model can simulate pressure‐induced diameter changes and myogenic tone, agonist‐induced vessel constrictions and relaxations, and conducted vasoreactivity. The model also predicts altered vascular reactivity from cellular changes reported in pathological conditions. Thus, the model was successful in integrating cellular mechanisms to describe vasoreactivity and is useful for relating reported changes in subcellular components to physiological responses in health and disease. [Supported by AHA grant NSDG043506N and NIH grant HL095101]