Arterial response to local mechanical variables in organ culture: The effects of circumferential and shear stress

The mechanical environment of arteries can be described in terms of global parameters (pressure, flow rate, and axial force) or local parameters (circumferential stress, shear stress, and axial strain). The global and local parameters are related by the equations of equilibrium, the flow equation, and the pressure-diameter response of the artery. From in vivo studies, it is known that arteries respond to changes in global parameters by changing dimensions, tone, and mechanical properties to restore the local parameters to homeostatic levels. This process of remodeling has also been studied in perfusion organ culture. To date, in vivo and organ culture studies of remodeling have subjected arteries to controlled changes of a single global parameter. Because arteries change dimensions and mechanical properties to restore the local mechanical environment to baseline levels, the local parameters vary over time. To address this limitation, a new approach has been developed to independently control local parameters by appropriately changing pressure and flow rate in organ culture. To illustrate the method, the effect of circumferential stress and shear stress on several biological markers of remodeling was studied.; Porcine carotid arteries were cultured for 3 days in a perfusion organ culture system to investigate the effects of circumferential stress and shear stress on arterial remodeling. For experiments varying circumferential stress, arteries were subjected to a circumferential stress of either 50 kPa or 150 kPa, while shear stress and axial stretch ratio were held at physiologic levels of 1.5 Pa and 1.5, respectively. For experiments varying shear stress, arteries were subjected to a shear stress of either 0.75 Pa or 2.25 Pa, while circumferential stress and axial stretch ratio were held at physiologic levels of 100 kPa and 1.5, respectively. Arterial remodeling was assessed by measuring biological marker including matrix synthesis, matrix metalloproteinase (MMP) activity, cell proliferation, and cell death.; The results showed that circumferential stress and shear stress have differential effects on arterial remodeling in organ culture. Circumferential stress induced a response in each of the biological markers. Matrix synthesis, as measured by 3H-proline incorporation, was significantly greater in arteries exposed to high circumferential stress. In contrast, MMP-2 activity was significantly less in high circumferential stress, while pro-MMP-9 activity was not significantly affected. The proliferation rates of smooth muscle cells and fibroblasts were significantly greater in arteries exposed to high circumferential stress. Smooth muscle cell death was also greater in high circumferential stress arteries. In contrast to circumferential stress, shear stress did not have a significant effect on the biological markers of remodeling measured in this study.; This novel approach can be used for the design and realization of different types of experiments focused on the effects of local mechanical parameters on arterial remodeling. This method can be used to determine the remodeling capacity of arterial cells or establish a ranking of local parameters to determine experimentally-motivated selection of growth laws for use in mathematical models. The results of this method can also be applied to the field of tissue engineering where understanding the effects of local mechanical factors on remodeling can offer a scientific basis for the design of optimal mechanical conditioning for vascular grafts.