Arteries respond to independent control of circumferential and shear stress in organ culture.

Arteries respond to changes in global mechanical parameters (pressure, flow rate, and longitudinal stretching) by remodeling to restore local parameters (circumferential stress, shear stress, and axial strain) to baseline levels. Because a change in a single global parameter results in changes of multiple local parameters, the effects of individual local parameters on remodeling remain unknown. This study uses a novel approach to study remodeling in organ culture based on independent control of local mechanical parameters. The approach is illustrated by studying the short term effects of circumferential and shear stress on remodeling-related biological markers. Porcine carotid arteries were cultured for 3 days at a circumferential stress of 50 or 150 kPa or, in separate experiments, a shear stress of 0.75 or 2.25 Pa. At high circumferential stress, matrix synthesis, smooth muscle cell proliferation, and cell death are significantly greater, but matrix metalloproteinase-2 (MMP-2) and pro-MMP-2 activity are significantly less. In contrast, biological markers measured were unaffected by shear stress. Applications of the proposed approach for improved understanding of remodeling, optimizing mechanical conditioning of tissue engineered arteries, and selection of experimentally motivated growth laws are discussed.

Sustained axial loading lengthens arteries in organ culture.

Although it has been recognized for many years that arteries in vivo exist under significant axial strain, studies of the adaptation of arteries to elevated axial strain have only recently been conducted. To determine the effects of sustained elevation of axial loading on arterial structure and function, axial stresses of 250 kPa or greater were applied to porcine common carotid arteries maintained in a perfusion organ culture system for 7 days at physiologic pressure and flow conditions. Our results demonstrated that axial stretch could lead to an increase in unloaded length that was proportional to the axial stretch ratio (stretched length divided by unloaded length) when the axial stretch ratio was above a threshold value of 2.14. Below this threshold, no significant length change occurred. Above this threshold, a significant increase in unloaded length (13 +/- 7%,) and the number of smooth muscle cell nuclei (20 +/- 7%) was observed. Permanent length change was associated with a significant decrease in axial stiffness, and the maximum elongation achieved was limited by rupture of the arterial wall. All tested arteries demonstrated good viability and strong vasomotor responses. These results show that arteries in organ culture can elongate under sustained axial loading.