Renal Microvascular Endothelial Heterogeneity In Sepsis: A Multiomics Approach

Sepsis is a complex disease that can lead to loss of kidney function. The processes underlying this are incompletely understood, leading to a lack of drugs to treat patients with sepsis. Endothelial cells play important roles during sepsis, for example by attracting white blood cells and regulating blood clotting. This makes endothelial cells interesting targets to treat sepsis. This thesis studies the responses of endothelial cells to sepsis in a laboratory setting, and describes how endothelial cells mount these responses and how they can be blocked using drugs. By combining innovative techniques, we furthermore created a complete molecular profile of different blood vessels in the kidney of healthy mice, and in mice with sepsis we identified unique molecular changes in the blood vessels that were highly dependent on the blood vessel segment studied. These outcomes indicate that blood vessels in the kidney and the resident endothelial cells exhibit different behaviour, both in health and during sepsis. We also identified multiple possible drug targets, which in the future may help block molecular changes from occurring in the blood vessels to ultimately treat or even prevent loss of kidney function during sepsis.