EFFECT OF SHEAR STRESS ON VASCULAR CELL TRANSCRIPTOMICS IN AN VITRO SETTING OF DRUG-ELUTING BIORESORBABLE VASCULAR SCAFFOLDS (BVS)

Background and Aims: Aim of this sub-study of H2020 EU funded InSilc project is to evaluate vascular cell response to different shear stress levels in an in vitro setting of Drug-eluting Bioresorbable Vascular Scaffolds (BVS).Methods: Human Coronary Artery Endothelial Cells (HCAECs) and Smooth Muscle Cells (HCASMCs) were cultured in dynamic conditions at flow rates corresponding to low and normal shear stress (1 and 20 dyne/cm2 respectively), with and without BVS under Everolimus 600 nM for 6 hours. Cell RNA-Seq and bioinformatics analysis provided gene modulation by direct comparison of shear stress conditions and Gene Ontology of biological processes shared by the two cell types.Results: A significant (> 3-fold) upregulation of MEOX2, related to proliferation and inflammation, in HCAECs, and of SEMA3E, with a role in migration and proliferation, in HCASMCs, is evidenced by low shear stress, with and without BVS. HCASMCs and HCAECs share four biological processes, two specifics for HCASMCs and two for HCAECs: three genes are constantly upregulated by low shear stress, BMP4 (neointima formation), HMOX1 (inflammation, proliferation, thrombosis) and SELE (lymphocytes homing in inflammation).Conclusions: Transcriptomic analysis of dynamic cell culture in vitro identifies candidate genes of low shear stress-related pro-restenotic and pro-thrombotic processes in an in vitro BVS setting, thus contributing to unravel the mechanism of vascular cell response to BVS stenting in vivo. This work is funded by the European Commission: Project InSilc, "In-silico trials for drug-eluting BVS design, development and evaluation" [GA number: 777119]. This article reflects only the author's view.