MicroRNA and mRNA Signatures in Ischemia Reperfusion Injury in Heart Transplantation |
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| Authors: | Liangyi Zhou Guoyao Zang Guangfeng Zhang Hansong Wang Xusheng Zhang Nathan Johnston Weiping Min Patrick Luke Anthony Jevnikar Aaron Haig Xiufen Zheng |
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| Affiliation: | 1. Department of Pathology, Surgery, Medicine, and Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.; 2. Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.; 3. Lawson Health Research Institute, London Ontario, Canada.; 4. Multiple Organ Transplant Program, London Ontario, Canada.; University of Toronto, Canada, |
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| Abstract: | Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. Several studies have demonstrated that microRNAs (miRNAs) are vital regulators of signalling pathways involved in I/R injury. The present study aims to quantify the altered expression levels of miRNA and mRNA upon I/R injury in a mouse heart transplantation model, and to investigate whether these miRNA can regulate genes involved in I/R injury. We performed heterotopic heart transplantation on mouse models to generate heart tissue samples with I/R and non-I/R (control). The expression levels of miRNAs as well as genes were measured in heart grafts by microarray and real time RT-PCR. miRNA alteration in cardiomyocytes exposed to hypoxia was also detected by qRT-PCR. We observed significant alterations in miRNA and gene expression profile after I/R injury. There were 39 miRNAs significantly downregulated and 20 upregulated up to 1.5 fold in heart grafts with I/R injury compared with the grafts without I/R. 48 genes were observed with 3 fold change and p<0.05 and 18 signalling pathways were enriched using Keggs pathway library. Additionally, hypoxia/reperfusion induced primary cardiomyocyte apoptosis and altered miRNA expression profiles. In conclusion, this is the first report on miRNA expression profile for heart transplantation associated with I/R injury. These findings provide us with an insight into the role of miRNA in I/R injury in heart transplantation. |
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