Abstract 1018: The Majority of Neointimal Cells in Arterial Allografts with or without Stents are of Recipient Origin
Allograft coronary disease (ACD) is the dominant cause of accelerated mortality after cardiac transplantation and remains relatively resistant to medical intervention. Controversy exists over the nature of the cells that constitute the progressively expanding neointima in ACD. While percutaneous implantation of metallic scaffolds (or stents) is the most efficacious revascularization strategy for ACD there is a disproportionately high incidence of stent renarrowing. We developed a novel rabbit model to test the hypothesis that the majority of neointimal cells in stented arterial allografts are host derived. Stents were inserted in sex-mismatched carotid allografts. Two weeks thereafter the neointima area was 58% greater in the stented vs. nonstented allograft segments (p=0.02) reflecting aggravated lesion formation in response to stenting. In situ hybridization for the Y-chromosome detected male cells in the non-stented and stented allograft neointima of female-to-male allografts. Quantitative PCR for the Y chromosome performed on laser capture microdissected neointima demonstrated the recipient origin in the non-stented and stented segments to be 72.1 ± 5.7% and 81.5 ± 4.2% of cells, establishing host cells as the primary source for in-stent neointima generation. Notably, the proliferation profiles of both the non-stented and stented segments of the allografts were low (2.7 ± 0.5%, 2.3 ± 0.2%; respectively), suggesting that increased neointimal burden likely reflected continual engraftment by host cells as opposed to proliferation of cells already populating the lesion. These data highlight an important role for host cells in the pathogenesis of allograft in-stent neointima formation and suggest alternative therapeutic approaches may be needed to improve clinical outcomes in the transplant population.