The implantation of a left ventricular assist device causes changes in the aortic miRNome and proteome - an integrative analysis

Abstract Background Left ventricular assist devices (LVAD) have been widely used and accepted to treat patients with end-stage heart failure. LVAD non-physiological blood flow velocity, wall shear stress distribution, vorticity current intensity, and vorticity flow generation affect the pathophysiology of vascular changes in aortic tissue. Purpose In this study, we performed multi-omics-based analysis of the aorta to identify molecular markers that could clarify vascular remodeling during LVAD support. Methods Aortic specimens from 48 patients (pair matched samples N=96) were excised during implantation and explantation of LVAD. Small RNA-Seq screening using Next Generation Sequencing and proteomic profile using Data-Independent Acquisition mass spectroscopy were conducted. Experimental and computational approaches, proteomics and transcriptomics data, were integrated and bioinformatics analyses were performed. Results The principal component analysis of miRNome and permutational multivariate analysis of variance of proteomic profile clearly segregated samples before and after LVAD support. We identified a total of 113 differently expressed (DE) miRNAs (61 up-regulated; Padj<0.05 and log2 fold change>|0.5|) after long-term LVAD support. Proteomic analysis identified in total 93 protein significantly changed (47 increased; Padj<0.05 and log2 fold change>|0.5|). Correlation analysis identified strong association between 270 proteins and 66 DE-miRNAs (Padj<0.05 and correlation coefficient>|0.7|). Gene Set Enrichment Analysis revealed, that predicted target genes of DE-miRNAs were mainly engaged in axon guidance, regulation of actin cytoskeleton, endocytosis, and MAP signaling pathway (Padj<0.05). DE-proteins participated mainly in ECM-receptor interaction, focal adhesion, and platelet activation (Padj<0.05). Conclusion Our study presents a network-based method of integrating microRNAs and proteome data and reveals molecular signatures that reflects aortic vascular remodeling due to LVAD treatment.PCA of miRNA DESeq2PCA of protemic profile