| First Author | Fukunaga N | Year | 2020 |
| Journal | Am J Transplant | Volume | 20 |
| Issue | 5 | Pages | 1262-1271 |
| PubMed ID | 31769924 | Mgi Jnum | J:328958 |
| Mgi Id | MGI:6881519 | Doi | 10.1111/ajt.15724 |
| Citation | Fukunaga N, et al. (2020) Protective role of Nrf2 against ischemia reperfusion injury and cardiac allograft vasculopathy. Am J Transplant 20(5):1262-1271 |
| abstractText | Ischemia-reperfusion injury (IRI) and cardiac allograft vasculopathy (CAV) remain unsolved complications post-heart transplant (Tx). The antioxidant transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) has been suggested to inhibit reactive oxygen species-mediated NF-kappaB activation. We hypothesized that Nrf2 inhibits NF-kappaB activation post-Tx and suppresses IRI and the subsequent development of CAV. IRI and CAV were investigated in murine heterotopic Tx models, respectively. Nrf2 wild-type (WT) and KO mice were used as donors. Sulforaphane was used as an Nrf2 agonist. In saline-treated animals following 24 hours of reperfusion in isogenic grafts, Nrf2-KO showed significantly less SOD1/2 activity compared with WT. Nrf2-KO displayed significantly high total and phosphorylated p65 expressions and percentage of cells with nuclear p65. mRNA levels of NF-kappaB-mediated proinflammatory genes were also high. Graft dysfunction, apoptosis, and caspase-3 activity were significantly higher in Nrf2-KO. In the allograft studies, graft beating score was significantly weaker in Nrf2-KO compared with WT. Nrf2-KO also demonstrated significantly more coronary luminal narrowing. In WT animals, sulforaphane successfully augmented all the protective effects of Nrf2 with increase of SOD2 activity. Nrf2 inhibits NF-kappaB activation and protects against IRI via its antioxidant properties and suppresses the subsequent development of CAV. |
