Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms

Autor: Min Young Park, Bala Murali Krishna Vasamsetti, Wan Seop Kim, Hee Jung Kang, Do-Young Kim, Byeonghwi Lim, Kahee Cho, Jun Seok Kim, Hyun Keun Chee, Jung Hwan Park, Hyun Suk Yang, Harikrishna Reddy Rallabandi, Sun A. Ock, Mi-Ryung Park, Heasun Lee, In-Sul Hwang, Jun-Mo Kim, Keon Bong Oh, Ik Jin Yun
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 2, p 751 (2021)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms22020751
Popis: Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.
Databáze: Directory of Open Access Journals
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