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Structural Adaptation of Microvessels in Disease States
Author(s) -
Threlkeld Elizabeth Fay,
Little Larissa,
Park Jea Young,
Varin Patrick,
Geddes John,
Sarang-Sieminski Alisha
Publication year - 2012
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.26.1_supplement.983.5
Subject(s) - disease , adaptation (eye) , vasodilation , neuroscience , shear stress , vascular disease , medicine , biology , cardiology , pathology , mechanics , physics
Hypertension, diabetes, and obesity are often associated with impaired microvascular function and structural adaptation. A.R. Pries and T.W. Secomb have developed a mathematical model of structural adaptation based on known physiological responses to shear stress, circumferential stress, and metabolic demand under healthy conditions. While this model captures key aspects of microvascular remodeling, it does not explicitly incorporate signaling pathways. As altered signaling pathways are a prominent feature of many disease states, in its current state this model cannot be used to predict the effects of diseases on vessel remodeling. Using the Pries and Secomb model as a framework, we have developed a model that incorporates relevant signaling pathways. In our model, diameter changes with nitric oxide, a vasodilator, and endothelin‐1, a vasoconstrictor, which are both functions of shear stress. Wall area changes with circumferential stress as well as the growth and death of vascular smooth muscle cells. Currently our model reflects the steady state trends in vessel geometry under normal conditions. Work is ongoing to further validate the model and examine vascular remodeling in disease states. Our long term goal is to improve the understanding of vascular adaptation in disease states and to create modeling tools which provide biologically testable hypotheses for experimentalists and clinicians.