Analysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound's toxic mode of action, by revealing specific pathway activation and... Show moreAnalysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound's toxic mode of action, by revealing specific pathway activation and other transcriptional modulations. Mapping changes in cellular behaviour to chemical insult, facilitates the characterisation of chemical hazard. In this study, we assessed the transcriptional landscape of mitochondrial impairment through the inhibition of the electron transport chain (ETC) in a human renal proximal tubular cell line (RPTEC/TERT1). We identified the unfolded protein response pathway (UPR), particularly the PERK/ATF4 branch as a common cellular response across ETC I, II and III inhibitions. This finding and the specific genes elaborated may aid the identification of mitochondrial liabilities of chemicals in both legacy data and prospective transcriptomic studies. Show less
Flow-based arterial spin labeling is a set of techniques used for non-contrast enhanced perfusion imaging. This work describes technical development done for application in body.
The endothelial glycocalyx is a thin layer consisting of sugar moieties on the endothelium of the whole vasculature. This layer has been shown to play a role in inflammation coagulation and... Show moreThe endothelial glycocalyx is a thin layer consisting of sugar moieties on the endothelium of the whole vasculature. This layer has been shown to play a role in inflammation coagulation and permeability in the vasculature. In this thesis we studied the structure and composition of the endothelial glycocalyx. We developed a model to induce an anti-inflammatory endothelial glycocalyx in vitro, using physiolgoical shear stress. Furthermore, we studied the role of this glycocalyx in the glomerular capillaries. Here we show that the endothelial glycocalyx contributes to the filtration barrier in the glomeruli. Consequently this implies that damage of this glycocalyx might be a first step in the development of vasculature-born renal failure, like in Type 2 diabetes. The other way around, we also studied the effect of renal failure on the systemic glycocalyx. Using a non-invasive method, we estimated glycocalyx thickness in the sublingual vasculature of patients with end stage renal disease and patients who received a kidney transplant. Interestingly, the endothelial glycocalyx was highly perturbed during end stage renal disease, but comparable to healthy controls after a kindye transplantation. Altogether the endothelial glycocalyx might be a central mediator in the development of both renal and cardiovascular disease. Show less
