Which can affect plaque vulnerability. Recent studies have highlighted that the placement of a stent against the artery wall may affect the arterial mechanical environment in very profound way. Stent application may directly injured endothelium through a mechanical stretching action that produces endothelial damage and denudation. Moreover, changes in flow patterns after stent positioning have been observed in experimental/computational flow study and include large-scale vortex formation and strut-spacing dependent flow stagnation. The low shear stresses associated with flow stagnation could likely induce, together with endothelial damage, vascular changes that are responsible of intimal hyperplasia, a leading cause of restenosis which occurs in 20–30% of patients within 6–12 months after primary stenting. Although several groups have reported that low shear stress compared to physiological one may affect gene expression MK-4827 profile of endothelial cells in different experimental systems, it is still unclear whether an invasive intervention like stent procedure may influence the transcriptional response of endothelium. To study the simultaneous effects of both changes in shear stress and stent application on endothelial gene expression, we have developed an experimental model of laminar flow bioreactor system with human cultured endothelial cells exposed or not exposed to stent procedure. RNA expression from different experimental conditions has been evaluated through the Affymetrix platform. The most relevant result of our work is that low shear stress in presence of stent is the experimental condition that modulates the highest number of genes. Indeed, we have observed that variations on genetic expression caused by flow plus stent procedure are higher than those caused by only flow or only stent application. Previous cellular model showed that physiological shear stress up-regulates genes with anti-atherogenic potential effect and down-regulates those with a pro-atherogenic behaviour, while the presence of low shear non-laminar flow is sufficient to induce a gene expression profile that pre-disposes the endothelium to the initiation and development of atherosclerotic lesions. However, it is unknown whether an invasive intervention like stent procedure, that introduces new structural changes in vascular compartment and in hemodynamic forces, may affect the transcriptional response of endothelial cells. To approach this lack of information, we studied the genetic expression profile of HUVEC submitted to different mechanical stimuli by Affymetrix technology searching for differently regulated genes in human endothelial cells. Using a bioinformatics tool, we found that genes involved in cytoskeleton organization and extracellular matrix are significantly down-expressed in disturbed shear stress. Most of them are linker proteins and regulators of intracellular microfilaments that mediate local trafficking of organelles and play a role in regulating the cell cytoskeleton and shape. Others are component of extracellular matrix or are regulators of its turnover.