Mechanobiology of the endothelium in vascular health and disease: in vitro shear stress models

In recent years, there has been growing evidence that vascular pathologies arise in sites experiencing an altered haemodynamic environment. Fluid shear stress (FSS) is an important contributor to vascular homeostasis and regulates endothelial cell (EC) gene expression, morphology, and behaviour through specialised mechanosensitive signalling pathways. The presence of an altered FSS profile is a pathological characteristic of many vascular diseases, with the most established example being the preferential localisation of atherosclerotic plaque development. However, the precise haemodynamic contributions to other vascular pathologies including coronary artery vein graft failure remains poorly defined. To evaluate potential novel therapeutics for the treatment of vascular diseases via targeting EC behaviour, it is important to undertake in vitro experiments using appropriate culture conditions, particularly FSS. There are a wide range of in vitro models used to study the effect of FSS on the cultured endothelium, each with the ability to generate FSS flow profiles through which the investigator can control haemodynamic parameters including flow magnitude and directionality. An important consideration for selection of an appropriate model of FSS exposure is the FSS profile that the model can generate, in comparison to the physiological and pathophysiological haemodynamic environment of the vessel of interest. A resource bringing together the haemodynamic environment characteristic of atherosclerosis pathology and the flow profiles generated by in vitro methods of applying FSS would be beneficial to researchers when selecting the appropriate model for their research. Consequently, here we summarise the widely used methods of exposing cultured endothelium to FSS, the flow profile they generate and their advantages and limitations in investigating the pathological contribution of altered FSS to vascular disease and evaluating novel therapeutic targets for the treatment and prevention of vascular disease.