Degradation of the internal elastic laminae in vein grafts of rats with aortocaval fistulae: potential impact on graft vasculopathy.

ABSTRACT

The internal elastic lamina (IEL) of vein grafts may be modified when exposed to arterialized hemodynamics. We investigated changes of the IEL in the inferior vena cava (IVC) of rats with aortocaval fistulae (ACF). In the IVC of ACF rats, both a markedly increased flow velocity and a mildly increased pressure were demonstrated. In the lower segment where hemodynamic changes were prominent, neointimal hyperplasia was prominently found. The IEL of the IVC in sham-operated rats, observed by confocal microscopy, was composed of parallel elastic fibers. In ACF rats, the IEL degenerated progressively after surgery. The elastic fibers were stretched and gradually became sparse, a change that was more prominent in the lower segment. Eight weeks after surgery, the IEL hardly existed in some areas of the lower segment. Electron microscopy revealed decreased densities and diameters of elastic fibers. Reverse transcriptase-polymerase chain reaction analysis revealed an up-regulation of potent elastases, cathepsins K and S, and matrix metalloproteinase-2 in the IVC of ACF rats. Results of immunohistochemical studies localized cathepsin expression predominantly to the luminal endothelium lining the IEL, suggesting involvement of elastinolysis in the degradation of the IEL. We demonstrated the degradation of the IEL in the vein graft of ACF rats, especially in the segment exposed to prominent hemodynamic changes. IEL degradation may contribute to the development of neointimal hyperplasia in vein grafts.