Identifying the mechanism of Na+-induced vascular inflammation

• Applicant: Professorin Dr. Kristina Kusche-Vihrog
• Subject Area: Anatomy and Physiology
• Term: from 2012 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 225755194

During the last years it was recognized that Na+, an apparently harmless ion, can be rated as high cardiovascular risk factor. Hypertension, stroke, coronary heart disease and inflammation are related to a high Na+ intake. Although the deleterious effects of a high Na+ intake are obvious, the underlying mechanisms are unknown. Vascular endothelial cells are exposed to the streaming blood and react sensitive to small increases of extracellular Na+. Specifically, Na+ concentrations above 140 mM directly affect the mechanical properties and thus the function of the outer layer of endothelial cells: it (i) damages the endothelial glycocalyx (eGC), a vasoprotective nano-barrier on top of endothelial cells, (ii) stiffens the cell cortex beneath the plasma membrane,(iii) reduces the release of nitric oxide (NO) and (iv) leads to increased adhesion of leukocytes to the endothelium. We postulate that Na+-induced reconstruction of the endothelium causes endothelial dysfunction and promotes vascular inflammation. Hence, central questions of the present project are how and why a small increase in Na+ has such a great impact on endothelial function. In the present project we aim to elucidate the link between Na+-dependent endothelial nanomechanics and its role in inflammatory processes within the cardiovascular system. A powerful combination of AFM (Atomic Force Microscopy)-based nano-techniques, fluorescence microscopy, molecular biological and protein biochemical methods will be employed to exactly quantify and analyze Na+-dependent endothelial nanomechanics and inflammatory processes. To translate these approaches in a physiological context state-of-the-art mouse models will be studied. With the present quantitative approach for the first time understanding of the link between Na+-induced vascular inflammation, endothelial nanomechanics and function will be provided which go far beyond the present knowledge.

• DFG Programme: Research Grants