Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Endothelial cell (EC) cytoskeleton is critical for EC adhesion and permeability. CSKR initiates permeability and influx of leukocytes which in turn leads to increased cytokine expression that stimulates EndoMT. First, we evaluated the impact of AR on the development of ECCSKR and EndoMT, and then showed their influence on the development of LF.
*Methods: A total of 66 patients were included in the study. Of 66 recipients 37 had AR episodes (Group 1) while 29 did not have AR (Group 2). To show the presence of CSKR and the development of EndoMT in ECs, paxillin, CD31, α-SMA, and TGF-β were studied. The intensity of leukocytes and macrophages were graded and highlighted with CD68, TNF-α, and TGF-β. Follow-up biopsies were analyzed for the development of LF during 18 months after biopsy.
*Results: The development of ECCSKR and EndoMT was found to be higher in Group 1 than Group 2 (p<0.01). Compared to patients without ECCSKR (0.5±0.4) and EndoMT (0.6±0.5) , the mean number of AR episodes was higher in recipients with ECCSKR (1.3±1.1) and EndoMT (1.1±0.8) (p<0.01). Patients who developed ECCSKR (90.3%) and EndoMT (86%) showed a higher incidence of LF than recipients who did not develop ECCSKR (23%) and EndoMT (16.7%) (p<0.001). Both TNF-α and TGF-β expression showed a positive correlation with the ECCSKR and EndoMT (p<0.001). Overall 10-year graft survival for patients with ECCSKR and EndoMT were 71% and 75% respectively, while it was 94% and 93% respectively for recipients without ECCSKR and EndoMT (p<0.01).
*Conclusions: EC activation during AR induces ECCSKR and EndoMT. With the development of ECCSKR, EC barrier may disrupt and permit leukocyte infiltration with large amounts of cytokines. ECCSKR and the mesenchymal transition of ECs with increased cytokines together induce graft loss due to the early development of LF.
To cite this abstract in AMA style:Ozdemir BH, Ozgun G, Soy EHAyvazoglu, Haberal N, Moray G, Haberal M. Endothelial Cell Cytoskeleton Rearrangement (ECCSKR) and Endothelial to Mesenchymal Transition (EndoMT) in Liver Allografts Following Acute Rejection (AR): Its Significance on the Development of Liver Fibrosis (LF) and Graft Survival [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/endothelial-cell-cytoskeleton-rearrangement-eccskr-and-endothelial-to-mesenchymal-transition-endomt-in-liver-allografts-following-acute-rejection-ar-its-significance-on-the-development-of-liver/. Accessed April 15, 2021.
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