Abstract 241: Novel Human Vein Xenograft Model

Résumé fourni par la source

Objectives: Approximately 30% of human vein grafts fail within the first year of implantation secondary to neointimal hyperplasia and adverse remodeling. This process has been difficult to study in animal models because of lack of a similar pathology. Therefore, we created a novel xenograft model where human saphenous vein was implanted into the infrarenal aorta of Rowett nude rats. Methods: Weekly ultrasound was performed before pressure perfusion fixation on postoperative day 28. Paraffin-embedded cross-sections were analyzed for human vs rat cells (using human-specific antibodies to mitochondria and Ku80) and for changes in wall thickening and extracellular matrix (ECM; Movat’s stain and antibodies to versican and aggrecan). Results: Successful human vein grafts (n=4) were ~150% larger than the native rat aorta as documented by photomicrograph (Figure 1A) and ultrasound (Figure 1B top) and showed appropriate arterial Doppler waveforms (Figure 1B bottom). Particularly robust neointimal, but also medial and adventitial, hyperplasia was observed in Movat’s stained cross-sections of the vein (Figure 1C). The neointimal layer was primarily ECM with relatively few cells. Surprisingly, the neointima stained poorly for versican, but was strongly positive for aggrecan. While neither human-specific antibody stained all cells, human cells were noted throughout the vein wall in similar numbers seen in human saphenous vein controls. Conclusions: This novel human vein xenograft model will be suitable for testing therapeutic strategies for decreasing neointimal hyperplasia leading to human vein graft failure. The novel observation of aggrecan in the neointima suggests new functions for aggrecan in the vascular setting.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.