Biology subjects

Daniel, H.

Publications and source records attributed to Daniel, H..

3 recordsLinked to original sources

bioRxiv2025

Altered endothelial mitochondrial Opa1-related fusion in mouse amplifies age-associated vascular and kidney damages

BackgroundCardiovascular diseases are the major cause of death worldwide and their frequency increases with age in association with progressive kidney damages. Endothelial cells (ECs) are early affected in cardiovascular diseases. Although energy production in ECs involves glycolysis, endothelial mitochondria play a role in modulating cellular signalling. A reduction in fusion protein Opa1 level in ECs decreases the vascular response to flow and increased oxidative stress in perfused kidneys. Thus, we hypothesized that reduced Opa1 expression contributes to vascular aging. MethodsWe used male and female mice with ECs specific Opa1 knock-out (EC-Opa1), and littermate wild-type (EC-WT) mice aged 6 (young) and 20 months (old). Mesenteric resistance arteries (MRA) and kidneys were collected for vascular reactivity and Western-blot analysis. ResultsIn old EC-Opa1 mice blood urea was greater than in age-matched EC-WT mice and MRA showed hypercontractilty and reduced endothelium-dependent relaxation. In kidneys, the mitochondria fission protein Fis-1 and the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1) were increase in old EC-Opa1 mice. The level of eNOS expression was greater in young EC-Opa1 mice and caveolin-1 expression greater in old EC-Opa1 mice. Moreover, in kidneys from EC-Opa1 old mice, NADPH-oxidase subunits gp91, p47 and p67 expression was greater than in age-matched EC-WT mice. No difference was observed between old and young EC-WT mice. ConclusionReduced mitochondrial fusion in mouse ECs altered mesenteric vascular reactivity and increased oxidative stress in aging kidneys. Thus, Opa1 might protect the vascular tree in target organs such as the kidney during aging.

physiology↗

bioRxiv2023

The HuMet Repository: Watching human metabolism at work

The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in health and disease, detailed documentation of healthy metabolic responses is needed but still scarce on a time-resolved metabolome-wide level. Here, we present the HuMet Repository, a web-based resource for exploring dynamic metabolic responses to six physiological challenges (exercise, 36 h fasting, oral glucose and lipid loads, mixed meal, cold stress) in healthy subjects. For building this resource, we integrated existing and newly derived metabolomics data measured in blood, urine, and breath samples of 15 young healthy men at up to 56 time points during the six highly standardized challenge tests conducted over four days. The data comprise 1.1 million data points acquired on multiple platforms with temporal profiles of 2,656 metabolites from a broad range of biochemical pathways. By embedding the dataset into an interactive web application, we enable users to easily access, search, filter, analyze, and visualize the time-resolved metabolomic readouts and derived results. Users can put metabolites into their larger context by identifying metabolites with similar trajectories or by visualizing metabolites within holistic metabolic networks to pinpoint pathways of interest. In three showcases, we outline the value of the repository for gaining biological insights and generating hypotheses by analyzing the wash-out of dietary markers, the complementarity of metabolomics platforms in dynamic versus cross-sectional data, and similarities and differences in systemic metabolic responses across challenges. With its comprehensive collection of time-resolved metabolomics data, the HuMet Repository, freely accessible at https://humet.org/, is a reference for normal, healthy responses to metabolic challenges in young males. It will enable researchers with and without computational expertise, to flexibly query the data for their own research into the dynamics of human metabolism.

biochemistry↗

bioRxiv2019

Characterization of bulk phosphatidylcholine compositions in human plasma using side-chain resolving lipidomics

Kit-based assays, such as AbsoluteIDQ p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally relevant information on the detailed fatty acid side chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side chain resolving Lipidyzer platform, analyzing 223 samples in parallel to the AbsoluteIDQ. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological datasets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data.

epidemiology↗