Acute mental stress drives vascular inflammation and promotes plaque destabilization in mouse atherosclerosis

Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.Aims: Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim to investigate the underlying mechanisms of these contributions since they remain largely unclear. Methods and results: Here, we show in humans and mice that leucocytes deplete rapidly from the blood after a single episode of acute mental stress. Using cell-tracking experiments in animal models of acute mental stress, we found that stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, lung, skin, and, if present, atherosclerotic plaques. Mechanistically, we found that acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells. Specifically, acute stress increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques. Conclusion: Our data show that acute mental stress rapidly amplifies inflammatory leucocyte expansion inside mouse atherosclerotic lesions and promotes plaque vulnerability.publishersversionPeer reviewe

Mechanical properties measured by Atomic Force Microscopy define health biomarkers in ageing C. elegans

Genetic and environmental factors are key drivers regulating organismal lifespan but how these impact healthspan is less well understood. Techniques capturing biomechanical properties of tissues on a nano-scale level are providing new insights into disease mechanisms. Here, we apply Atomic Force Microscopy (AFM) to quantitatively measure the change in biomechanical properties associated with ageing Caenorhabditis elegans in addition to capturing high-resolution topographical images of cuticle senescence. We show that distinct dietary restriction regimes and genetic pathways that increase lifespan lead to radically different healthspan outcomes. Hence, our data support the view that prolonged lifespan does not always coincide with extended healthspan. Importantly, we identify the insulin signalling pathway in C. elegans and interventions altering bacterial physiology as increasing both lifespan and healthspan. Overall, AFM provides a highly sensitive technique to measure organismal biomechanical fitness and delivers an approach to screen for health-improving conditions, an essential step towards healthy ageing

Characterisation of metabolic mutants with respect to their growth behaviour with different oxygen availabilities

Regulation of aerobic and anaerobic metabolism in E. coli is a well investigated topic and the regulators responsible for the switch between these growth scenarios are known. Several regulatory proteins activate or repress the expression of enzymes depending on the availability of oxygen. These enzymes are either directly involved in respiration or are metabolic enzymes like enzymes of the TCA-cycle. There is a complex interaction between the regulatory and the metabolic network which is until now not completely elucidated. We are aiming to an improved understanding of this interaction by applying a systems biological approach that couples quantitative biological experiments with mathematical modelling. Characterisation of metabolic and regulatory mutants should lead to a deeper understanding of the redox regulation in E. coli. In these mutants enzymes were knocked-out which catalyse for example specific reactions of the TCA-cycle. Mutant strains were characterised in a chemostat under defined conditions to obtain comparable results. Metabolic reactions were examined via measurement of oxygen consumption rates, production of fermentation products, biomass, redox state of the cells and energy charge, as well as the expression rate of specific enzymes via Real-Time PCR. Different oxygen concentrations were adjusted – aerobic, microaerobic and anaerobic conditions – and the reaction of the mutant strains to the changing environment was compared to the reaction of the wild type strain

Glucose transport in Escherichia coli mutant strains with defects in sugar transport systems

In Escherichia coli, several systems are known to transport glucose into the cytoplasm. The main glucose uptake system under batch conditions is the glucose phosphoenolpyruvate:carbohydrate phosphotransferase system (glucose PTS), but the mannose PTS and the galactose and maltose transporters also can translocate glucose. Mutant strains which lack the enzyme IIBC (EIIBC) protein of the glucose PTS have been investigated previously because their lower rate of acetate formation offers advantages in industrial applications. Nevertheless, a systematic study to analyze the impact of the different glucose uptake systems has not been undertaken. Specifically, how the bacteria cope with the deletion of the major glucose uptake system and which alternative transporters react to compensate for this deficit have not been studied in detail. Therefore, a series of mutant strains were analyzed in aerobic and anaerobic batch cultures, as well as glucose-limited continuous cultivations. Deletion of EIIBC disturbs glucose transport severely in batch cultures; cyclic AMP (cAMP)-cAMP receptor protein (CRP) levels rise, and induction of the mgl operon occurs. Nevertheless, Mgl activity is not essential for growth of these mutants, since deletion of this transporter did not affect the growth rate; the activities of the remaining transporters seem to be sufficient. Under conditions of glucose limitation, mgl is upregulated 23-fold compared to levels for growth under glucose excess. Despite the strong induction of mgl upon glucose limitation, deletion of this transport system did not lead to further changes. Although the galactose transporters are often regarded as important for glucose uptake at micromolar concentrations, the glucose as well as mannose PTS might be sufficient for growth at this relatively low dilution rate