Development of an Agent-based Model of Arterial Wall Remodeling in Response to Hypertension

Bryan C. Thorne (1), Heather Hayenga (2), Jay Humphrey (2), and Shayn M. Peirce (1)

(1) University of Virginia, Charlottesville, VA and (2) Texas A&M University, College Station, TX

TITLE: Development of an Agent‐Based Model of Arterial Wall Remodeling in Response to Hypertension

ABSTRACT: When faced with increased mechanical stress caused by hypertension, smooth muscle cells in an artery wall proliferate and lay down increased amounts of collagen. This leads to thickening of the artery and returns hoop stress to its optimal level. Thickening and stiffening of the artery wall may also lead to propagation of the increased pressure wave further down the vascular tree, causing remodeling at other sites. We describe the development and initial results of an agent‐based model (ABM) of smooth muscle and endothelial cell reactions to mechanical stresses in an artery wall. Mechanosensing by the cells leads to changes in production of biochemical growth factors, such as PDGF and TGF‐beta. These growth factors, in turn, control proliferation and differentiation of smooth muscle cells, as well as production of extracellular matrix (ECM) and ECM modifiers (e.g. collagen and metalloproteases). Changes in the physical composition of the vessel wall (i.e. “vascular remodeling”) impact the mechanical stress sensed by the cells. For improved calculation of stresses sensed by cells, we have designed an ABM that is coupled to a continuum mixture model (CMM) developed by our collaborators at Texas A&M that predicts hoop stress and shear stress in a vessel wall based on the cellular and extracellular composition of the vessel wall.

Initial results from the ABM show a stable, homeostatic vascular wall at static, physiological pressures. The model is insensitive to short term elevations in blood pressure, yet demonstrates proliferation and collagen synthesis in response to longer term hypertension. Once coupled with the CMM, we believe that this model will demonstrate increased accuracy in predicting vascular wall remodeling in response to elevated mechanical stresses.

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