title: MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation.
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.
authors.affiliation: Department of Pathology, Surgery, Medicine, and Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Liangyi
authors.initials: L
authors.lastname: Zhou
authors.forename: Guoyao
authors.initials: G
authors.lastname: Zang
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.forename: Xusheng
authors.initials: X
authors.lastname: Zhang
authors.forename: Nathan
authors.initials: N
authors.lastname: Johnston
authors.forename: Weiping
authors.initials: W
authors.lastname: Min
authors.forename: Patrick
authors.initials: P
authors.lastname: Luke
authors.forename: Anthony
authors.initials: A
authors.lastname: Jevnikar
authors.forename: Aaron
authors.initials: A
authors.lastname: Haig
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger