THE IMPLANTATION OF LVAD CAUSES CHANGES IN THE AORTIC MIRNOME AND PROTEOME

Background: Left ventricular assist devices (LVAD) have been widely used and accepted to treat patients with end-stage heart failure (HF). 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 employed multi-omics-based analysis of the aorta to identify molecular markers that could clarify vascular remodelling during LVAD support.
Methods: A group of 48 patients (average age 48.7 ± 13.6 years; 18.4% female; mean INTERMACS (profile 2.7) was studied. All patients had LVAD (HeartMate 3TM) implanted as a bridge to transplantation. Tissue specimens (96 pair-matched samples) were taken from the ascending aorta during LVAD implantation and explantation. Small RNA-Seq screening using Next Generation Sequencing and proteomic profile using Data-Independent Acquisition mass spectroscopy were conducted.
Results: We found that the most upregulated miRNAs in explanted samples target genes involved in extracellular matrix (ECM) remodelling, collagen deposition, smooth muscle cell (SMC) and endothelial cell (EC) proliferation. Gene enrichment analysis of both omics suggests highly differentiated cell cycle and transcriptional regulation in the explanted samples. Enriched Gene Ontology (GO) terms were related to apoptotic mitochondrial changes, mitochondrial membrane organization, the mitochondrial matrix and collagen trimer.
Conclusion: The GO-enriched results suggest significant changes in mitochondria. Considering the interplay between ECM and mitochondria in this context, further research is needed to investigate the impact of non-physiological flow patterns on vascular function and vascular energy metabolism.