The blood vessels of the body often change in order to maintain health. This process, called "vascular remodeling" is a long-lasting alteration in structure, geometry, or mechanical properties of adult blood vessels. Both too much and too little remodeling occur in different diseases, for example, in high blood pressure and in the formation of an aneurysm. In addition to the forces of blood on the vessels, the cells also pull on the vessel to maintain function. The investigators recently showed that the cells change how they pull on the cell walls in response to diet and age even when the blood forces aren't changed. The experimental results of changes in the vessels walls caused by the cells was successfully modeled for normal mice and makes a prediction on how the blood vessels will change in experimental mice missing an important chemical message in the blood vessels (nitric oxide deficient mice). This project is to experimentally test the model prediction to determine whether the model is correct. The educational and outreach aspects of the project include undergraduate and graduate training in biomechanics and mechanobiology, course development, research experiences for high school students, and outreach to high school teachers in STEM subjects through Project Lead the Way. Blood vessel remodeling is a key part of common vascular diseases. The research project will improve the ability to predict disease progression and improve public health.
Theoretical and computational approaches to analyze vascular remodeling using continuum mechanics have often suffered from a lack of experimental data to provide quantitative descriptions of active biological contributions to remodeling, such as the contribution of activated smooth muscle cells. By providing an innovative, tightly integrated framework incorporating both experimental and mathematical analysis, this shortfall will be addressed in the context of age-related vascular remodeling and its response to endothelial dysfunction. This work is potentially transformative in its ability to identify and characterize a novel mechanism of age-related vascular remodeling independent of hemodynamic changes, and to provide a theoretical and computational framework with the power to predict a wide spectrum of remodeling outcomes, including reorientation of collagen fibers, and their effects on vascular biomechanics. The time course of aortic remodeling will be characterized in terms of changes in vessel geometry, composition, and collagen fiber orientation. Hemodynamic contributions to remodeling will be tracked by measuring blood pressures and volumetric flow rates. Nitric oxide synthase 3 protein expression and nitric oxide production by aortic segments will be used as measures of endothelial function. The researchersa will develop and independently validate a mathematical framework that incorporates a combined passive and active constitutive model of arterial tissue to explain the process by which changes in smooth muscle cell contraction contractile tone drive vascular remodeling in the absence of significant hemodynamic changes.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
