P089 : IS THERE A LINK BETWEEN TRANSCRIPTION AND HLA IN CARDIAC TRANSPLANTATION?

Abstract

Heart transplantation has evolved as the “gold standard” therapy for patients with end-stage heart failure (HF). Although mechanical circulatory support technology is improving, heart transplantation remains the preferred treatment. The mean risk factors for HF include environmental and genetic components. The intricate patterns of gene expression, during normal and disease states, are governed by elaborate signaling pathways that converge on the transcriptional mechanism. The general transcriptional mechanism can be recruited to promoters by Mediator complex (MED). MED is a large multi-subunit complex functioning to integrate diverse cellular signals by multiple mechanisms including recruitment of RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. Several MED subunits are involved in many human pathologies, including heart diseases. Particularly, some subunits like MED13 and MED13L are altered in congenital heart diseases. Similarly, MED30 mutation can lead to lethal cardiomyopathy in a mouse model. To gain further insights, we have collected 12 human left atrium samples, which were acquired from hearts of 6 donors and 6 recipients during transplant intervention. Patients were affected by hypertrophic or dilated idiopathic cardiomyopathy. From these samples we have isolated RNA and started to analyze the expression patterns of MED subunits by real-time RT-PCR with specific oligonucleotides. Possible interactions between human leukocyte antigen (HLA) profile and MEDs are under investigation. Furthermore, RNA-seq analysis of samples from both donors and recipients is ongoing in our laboratory and whole transcriptome data will be also shown. Our preliminary data confirm that some MED subunits are altered in diseased hearts compared to healthy donor biopsies. The identification of such alterations can lead to novel therapeutic targets regulating MED subunits, and HLA in advanced HF.