Studying the long-term impact of continuous-flow left ventricular assist device (CF-LVAD) offers an opportunity for a complex understanding of the pathophysiology of vascular changes in aortic tissue in response to a nonphysiological blood flow pattern. Our study aimed to analyze aortic mRNA/miRNA expression changes in response to long-term LVAD support. Paired aortic samples obtained at the time of LVAD implantation and at the time of heart transplantation were examined for mRNA/miRNA profiling. The number of differentially expressed genes (Pcorr < 0.05) shared between samples before and after LVAD support was 277. The whole miRNome profile revealed 69 differentially expressed miRNAs (Pcorr < 0.05). Gene ontology (GO) analysis identified that LVAD predominantly influenced genes involved in the extracellular matrix and collagen fibril organization. Integrated mRNA/miRNA analysis revealed that potential targets of miRNAs dysregulated in explanted samples are mainly involved in GO biological process terms related to dendritic spine organization, neuron projection organization, and cell junction assembly and organization. We found differentially expressed genes participating in vascular tissue engineering as a consequence of LVAD duration. Changes in aortic miRNA levels demonstrated an effect on molecular processes involved in angiogenesis.

2nd Department of Surgery Department of Cardiovascular Surgery 1st Faculty of Medicine Charles University 121 08 Prague Czech Republic

3rd Department of Internal Medicine 1st Faculty of Medicine Charles University 121 08 Prague Czech Republic

Department of Cardiovascular Surgery Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Department of Physiology 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Experimental Medicine Centre Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Laboratory of Gene Expression Institute of Biotechnology CAS BIOCEV 252 50 Vestec Czech Republic

Laboratory of Informatics and Chemistry Faculty of Chemical Technology University of Chemistry and Technology 166 28 Prague Czech Republic

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