Interest Group on Endothelial Plasma Membrane Lipidome (EndotheliOme)

Why endothelial plasma membrane lipidomics

Endothelial cells (EC) lining blood vessels play a pivotal role in regulating and maintaining vascular health. Being constantly and continuously exposed to mechanical and other environmental (oxidative) stimuli, EC can “sense” changes to their surrounding milieu rapidly altering the endothelial plasma membrane lipid composition, organisation and fluidity. Changes to the membrane’s lipid environment and physical properties, trigger the activation of membrane proteins and downstream signaling pathways hinting to EC plasma membranes with mechanosensing response (“mechanosensors”). Though impairment of EC mechanoresponses has been implicated in the onset and progression of vascular diseases, to date the lipid remodeling undergone by EC plasma membrane in adaptation to short- (mechanical, thermal, smoking) and long-term stimuli (age and disease), their impact on the exchange of solutes (drugs, gases, metabolites) across the endothelial barrier and the implications to membrane-driven trafficking and signaling events remains remarkably poorly understood.

Given the rising incidence of diet-related diseases (obesity, diabetes, hypertension) in adolescents and young adults and the burden of vascular disorders (stroke, myocardial infarction, atherosclerosis, retinopathy, nephropathy) in an increasingly aging society, prompts immediate action to advance knowledge on endothelial plasma membrane lipidome in health and disease.

This can only be achieved through an integrated and concerted effort between analytical chemists, biochemists, cell biologists, biophysicists, clinicians, bioinformatics and computational chemists able to advance and translate knowledge in (patho)physiological scenarios such as hypertension, atherosclerosis, vascular aging, neurodegenerative diseases, cancer and many others.

Goals

Build up a collaborative network of researchers and professionals across Europe who share a common interest in advancing EC membrane field, fostering cross-disciplinary collaboration and promoting knowledge exchange in the field of lipid and vascular biology.

Networking activities will leverage EC membrane lipidomics, including membrane lipid analysis, lipid metabolism and biochemistry, membrane biophysics and imaging, and the role of lipids in human health and disease, and hence advance, and promote knowledge and scientific innovation with colleagues in pharmaceutical, clinicians and vascular biology areas and ultimately contributing to minimize the risk and severity of vascular complications in an increasingly aging society.

Main lines of interest

  • Mapping the lipid remodeling of endothelial plasma membranes in health and disease
    Gain insights on 1) the endothelial plasma membrane lipidome of primary EC (heart, brain, lungs) collected from diseased donors (hypertension, obesity, cardiovascular diseases); and 2) characterize the lipid asymmetry in endothelial plasma membrane apical and basolateral leaflets (e.g. commercial kits, ultracentrifugation or “peeling-off” protocols). Based on the endothelial lipidome in human EC and the current knowledge on EC models grown under hyperoxia and static flow conditions gain insights on the suitability and limitations of in vitro cell models.
  • Expansion of sphingolipidome coverage
    Sphingolipids together with sterols are the major lipids in endothelial plasma membranes being involved in the formation of specialized platforms (“lipid-rafts”) that serve as anchors to membrane proteins involved in membrane trafficking and signaling. Sphingolipids containing complex glycosylated chains that confer a hydrophilic character lead to poor extraction recoveries when using 2-phase solvent systems. To improve knowledge on the whole sphingolipidome, optimization of (glyco)sphingolipid analysis protocols in biological samples is essential, moving towards the standardization of protocols to ensure inter-laboratory consistency and reproducibility.
  • Lipid oxidation in vascular inflammation
    As part of the lipid remodeling in age and disease, conduct in-depth screening on the oxylipidome (oxysterols, oxidized phospholipids) present in endothelial plasma membranes in health and disease and the implications on redox-mediated signaling in inflammation. In parallel, the identification and quantification of membrane protein-oxidised phospholipid adducts and the relationship in membrane protein function, and role in molecular mechanism of redox-mediated signaling
  • Healthy diets for functional membranes
    Adherence to plant-based eating patterns including Mediterranean Diets and Dietary Approaches to Stopping Hypertension (DASH) are widely recognized as valuable nutritional strategies in the management and progression of chronic diseases; this prompts in-depth investigation on the interaction of bioactive plant-based phytochemicals with membrane lipids, their impact on the biophysical properties of cholesterol-rich membranes, their role in structure/function of membrane proteins involved in sugar and lipid metabolism, and their potential to restore endothelial function and manage vascular diseases.
  • Biophysics of endothelial cholesterol-rich lipid assemblies
     Understand the impact of lipid remodeling on the distribution and co-localisation of lipids across the lipid bilayer (lipid asymmetry) as well as their lateral organisation and its implications on membrane’s biophysical parameters (lipid order, hydration, fluidity) in cholesterol-rich models (e.g. GPMVs) to infer on in vivo membrane permeability and exchange of solutes (metabolites, drugs, and gases) in disease scenarios.
  • Spatio-temporal architecture in vascular (mechano)biology
    Using time-lapse cell imaging techniques, understand how lipid remodeling in adaptation to disease impacts the plasma membrane architecture and membrane proteins to monitor intracellular signaling and membrane trafficking (endocytosis and exocytosis events) particularly the scavenger receptor-mediated endocytosis of oxLDL by endothelial cells.
  • Plasma membrane lipidomics driving molecular simulations
    Using knowledge from the endothelial plasma membrane lipidomics, streamline computational modeling to study the conformation of membrane proteins (e.g. eNOS, GLUTs, GPCR, integrins, OATs) involved in sugar and lipid metabolism, and vascular function leading to new therapeutic targets and tailoring the design of new drugs.
  • Education and Training
    Training courses (webinars) on cell membrane isolation, standardization lipid nomenclature and lipid analysis; lipid extraction; characterisation of cholesterol-rich membrane models by microscopy techniques: challenges and limitations;

    Exchange of students (STSMs, Erasmus, DAAD, …)

  • Exploitation and Communication
    COST action newsletters, scientific meetings, grant application,

Who we want to target

Academia – research and education/training



Stakeholders – Pharmaceutical industry (vaccines/antibodies), drug development and drug delivery, bioinformatics, nanoparticle research;

Activities

  • Website
  • Webinars, seminars, and symposia within conferences
  • Joint research, joint funding application, COST actions
  • Joint researcher training (doctoral researchers and postdocs)
  • Promote researcher mobility, student & teacher exchange (ERASMUS, EC2U, and other)

CA19105 – Pan-European Network in Lipidomics and EpiLipidomics

CSO Approval Date: 24 March 2020
Start Date: 13 October 2020
End Date: 12 October 2024
EpiLipidNET aims to build and maintain a multidisciplinary pan-European network of researchers, clinicians and enterprises working in the field of lipidomics and epilipidomics to boost a hub of research excellence, advanced knowledge and technology transfer, to promote high level of training for young researchers and facilitate clinical translation.