Severe heart failure leads to the implantation of a left ventricular assist device (LVAD) in patients waiting for a heart transplant. These pumps induce a change in the blood flow regime: from a physiological pulsatile flow to a pathological and continuous flow with higher shear stress, provoking bleedings, mostly gastrointestinal, in 35% of patients.

The aim of this study was to submit aortic endothelial cells to continuous and pulsatile flow to understand how the type of flow impacts their phenotype.

Aortic endothelial cells were cultured under flow using the IBIDI pump system. Cells were preconditionned with a continuous flow at low shear stress (10dyn/cm²) before applying continuous or pulsatile flow at high shear stress (35dyn/cm²) for 24hours. Culture media were collected to measure the von Willebrand factor (VWF) secretion by ELISA and RNA extraction was performed for RNA-sequencing.

Continuous flow condition led to a significant decrease of VWF release without difference in gene expression. Continuous vs pulsatile flow conditions were analyzed by RNA-sequencing (Fig. 1A). The top 3 genes increased in continuous vs pulsatile flow condition are SERPINB2, IL1RL1, CXCL8. The 3 most significantly enriched biological pathways for upregulated genes are “Positive regulation of apoptotic process”, “response to lipopolysaccharide”, “response to xenobiotic stimulus” (Fig. 1B). The top 3 genes decreased in continuous vs pulsatile flow are VIPR1, DEPP1, ABCG1 and the 3 most significantly enriched biological pathways for downregulated gene are “Tube morphogenesis”, “negative regulation of c ell population proliferation” and “regulation of angiogenesis” (Fig. 1C). In a network analysis, results indicated that high shear continuous flow led to a decreased gene expression of actors of the Notch pathway an increased expression of genes involved in oxidative stress.

This study shows significant impact of continuous vs pulsatile flow on aortic endothelial cells biology at high shear stress in vitro.