MicroRNA and mRNA Signatures in Ischemia Reperfusion Injury in Heart Transplantation

作者：Zhou, Liangyi; Zang, Guoyao; Zhang, Guangfeng; Wang, Hansong; Zhang, Xusheng; Johnston, Nathan; Min, Weiping; Luke, Patrick; Jevnikar, Anthony; Haig, Aaron; Zheng, Xiufen^*

来源：PLos One, 2013, 8(11): e79805.

DOI：10.1371/journal.pone.0079805

• NITRIC-OXIDE SYNTHASE
• DOWN-REGULATION
• UP-REGULATION
• EXPRESSION
• PROTECTS
• TARGET
• CARDIOPROTECTION
• PRESERVATION
• APOPTOSIS
• SURVIVAL

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.

• 出版日期2013-11-20
• 单位浙江大学