Fall 2019 – Implications of Simple Growth Rule to Predict Endothelial Shear Stresses and Radii of Cerebral Vessels

Critical disease states such as atherosclerosis, vasospasm, and ischemic stroke have been associated with endothelial dysfunction. Mechanotransduction studies have revealed that blood vessel radii increase acutely and chronically to increases in endothelial shear stress. Experimental approaches to investigate mechanotransduction in the cerebrovasculature are limited, because changes in radii affect endothelial shear stresses through altered hemodynamics. Conversely, changes in endothelial shear stresses affect radii through growth and remodeling. Conventional mathematical models that predict how cerebrovascular networks adapt can predict radii, but they assume a constant endothelial shear stress set point. However, similar limitations have been addressed by investigators who incorporated mechanotransduction by assuming that radius increases with endothelial shear stress. Therefore, the purpose of the present work is to modify a standard cerebrovasculature model with a simple growth rule to predict both endothelial shear stress and radii of cerebral vessels. We will be developing the model and comparing predictions to previously published data. Because this model provides a framework to translate basic science in molecular and cellular mechanotransduction involving vascular endothelial cells into growth of vessels over time, we will be looking for novel insights into the development and treatment of diverse cerebrovascular diseases.