Biomechanical determinants of endothelial permeability assessed in standard and modified hollow-fibre bioreactors

Abstract

Effects of mechanical stress on the permeability of vascular endothelium are important to normal physiology and in the development of atherosclerosis. Here we elucidate novel effects using commercially available and modified hollow-fibre bioreactors, in which endothelial cells form confluent monolayers lining plastic capillaries with porous walls, contained in a cartridge. The capillaries were perfused with a near-aortic waveform, and permeability was assessed by the movement of rhodamine-labelled albumin from the intracapillary to the extracapillary space. Permeability was increased by acute application of shear stress and decreased by chronic shear stress compared with a static control: this has previously been shown only for multidirectional flows. Increasing viscosity reduced permeability under both acute and chronic shear; since shear rate remained unchanged, these effects resulted from altered shear stress. Reducing pulsatility increased permeability, contrary to the widely held assumption that flow which is highly oscillatory causes endothelial dysfunction. Chronic convection across the monolayer increased effective permeability more than could be explained by the addition of advective transport, contrary to results from previous acute experiments. The off-the-shelf and modified bioreactors provide an excellent tool for investigating the biomechanics of endothelial permeability and have revealed novel effects of flow duration, viscosity, pulsatility and transmural flow.