Aquaporin 4 blockade improves survival of murine heart allografts subjected to prolonged cold ischemia

• DOI: 10.1111/ajt.14624
• Publication Date: 2017-12-16T10:57:48Z
• Authors: Katayoun Ayasoufi; Naoki Kohei; Michael Nicosia; Ran Fan; George W. Farr; Paul R. McGuirk; Marc F. Pelletier; Robert L. Fairchild; Anna Valujskikh
• Keywords: Immunosuppression

Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there need novel approaches improve outcomes of marginal allografts and expand the pool donor organs suitable transplantation. Aquaporins (AQPs) are family water channels that facilitate homeostasis, tissue injury, inflammation. We tested whether inhibition AQP4 improves survival fully MHC-mismatched murine cardiac subjected 8 hours CIS. Administration small molecule inhibitor during heart collection short-time posttransplantation viability graft cells, diminishes donor-reactive T cell responses, extends allograft absence other immunosuppression. Furthermore, synergistic with cytotoxic lymphocyte-associated antigen 4-Ig prolonging 8-hour CIS allografts. blockade markedly reduced proliferation cytokine production vitro, suggesting improved at least part mediated through direct effects on cells. These results identify AQPs as promising target diminishing donor-specific alloreactivity improving high-risk organ transplants.