The Role of Circular RNA HIPK3 in Ischemia Reperfusion Injury During Heart Transplantation
Abstract
There are currently ~600,000 Canadians with end stage heart failure. Although medications are effective, the ideal treatment would be heart transplantation. Loss of blood (ischemia) to the organ during preservation and restoration of blood flow (reperfusion) leads to ischemia reperfusion injury (IRI) which can lead to cell death. Circular RNA is a new type of non-coding RNA forming a covalently closed loop single stranded RNA. Evidence suggests circular RNA Hipk3 (circHIPK3) generated from exon 2 of the Hipk3 gene is involved in many pathologies. However, the role of circHIPK3 in IRI has not been investigated. Using our in vitro IRI model, we showed that CircHIPK3 expression is increased during IRI and knockdown increased cell death. In addition, circHIPK3 knockdown exacerbated pro-apoptotic Bax mRNA levels, caspase 3 activation and MLKL phosphorylation. We also observed no significant changes in inflammatory response following circHIPK3 knockdown and IRI. In conclusion, the loss of circHIPK3 expression exacerbates apoptosis and necroptosis during IRI and is crucial to cell survival.