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Rejection severity directly correlates with myocyte apoptosis in pig-to-baboon cardiac xenotransplantation.

Weaver, JGR; McGregor, CGA; Tazelaar, HD; Badley, AD; (2005) Rejection severity directly correlates with myocyte apoptosis in pig-to-baboon cardiac xenotransplantation. J Heart Lung Transplant , 24 (7) pp. 841-847. 10.1016/j.healun.2004.05.017.

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Abstract

BACKGROUND: The process by which cardiac myocytes die during xenograft rejection is incompletely understood. The presence of cardiac myocyte apoptosis in discordant xenotransplant models has been noted, yet no investigators have examined whether a relationship between myocyte apoptosis and rejection severity exists. Thus, we chose to further investigate this observation. METHODS: Eight explanted pig-to-baboon cardiac grafts with varying severities of rejection, as determined by hematoxylin and eosin histology, were examined for apoptosis by transmission electron microscopy (TEM) and TUNEL (terminal deoxynucleotide transferase-mediated digoxigenin-dUTP nick-end labeling) immunohistochemistry. In addition, Western blot analysis for the cleavage of the apoptosis regulatory proteins pro-caspase 8 and 3 was performed. RESULTS: Transmission electron microscopy revealed that a severely rejected graft displayed widespread condensation of nuclear chromatin, which is a characteristic morphologic feature of apoptosis. TUNEL staining verified this observation and allowed for the quantification of myocyte apoptosis in each graft. Subsequent linear regression analysis of the extent of myocyte apoptosis and rejection severity revealed a direct correlation (R(2)=0.757, p=0.005). In addition, Western blot analysis demonstrated that myocyte apoptosis involves the cleavage of pro-caspase 8 and 3. CONCLUSIONS: Myocyte death in rejecting pig-to-baboon cardiac xenografts occurs through an apoptotic pathway and directly correlates with the severity of graft rejection. Further studies aimed at elucidating the apoptotic stimulus are therefore warranted. Moreover, our data suggest that antiapoptotic strategies may be of benefit in the treatment of xenograft rejection.

Type: Article
Title: Rejection severity directly correlates with myocyte apoptosis in pig-to-baboon cardiac xenotransplantation.
Location: United States
DOI: 10.1016/j.healun.2004.05.017
Keywords: Animals, Apoptosis, Graft Rejection, Heart Transplantation, In Situ Nick-End Labeling, Muscle Cells, Papio anubis, Swine, Transplantation, Heterologous
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/1373688
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