title: Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.
abstract: High-throughput biochemical profiling has led to a requirement for advanced data interpretation techniques capable of integrating the analysis of gene, protein, and metabolic profiles to shed light on genotype-phenotype relationships. Herein, we consider the current state of knowledge of endothelial cell (EC) metabolism and its connections to cardiovascular disease (CVD) and explore the use of genome-scale metabolic models (GEMs) for integrating metabolic and genomic data. GEMs combine gene expression and metabolic data acting as frameworks for their analysis and, ultimately, afford mechanistic understanding of how genetic variation impacts metabolism. We demonstrate how GEMs can be used to investigate CVD-related genetic variation, drug resistance mechanisms, and novel metabolic pathways in ECs. The application of GEMs in personalized medicine is also highlighted. Particularly, we focus on the potential of GEMs to identify metabolic biomarkers of endothelial dysfunction and to discover methods of stratifying treatments for CVDs based on individual genetic markers. Recent advances in systems biology methodology, and how these methodologies can be applied to understand EC metabolism in both health and disease, are thus highlighted.
authors.affiliation: Center for Systems Biology, University of Iceland , Reykjavik , Iceland.
authors.forename: Sarah
authors.initials: S
authors.lastname: McGarrity
authors.affiliation: Department of Pharmacology and Toxicology, School of Health Sciences, University of Iceland , Reykjavik , Iceland.
authors.forename: Haraldur
authors.initials: H
authors.lastname: Halldórsson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Sinopia Biosciences Inc., San Diego, CA, USA.
authors.forename: Sirus
authors.initials: S
authors.lastname: Palsson
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Department of Biochemistry and Molecular Biology, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
authors.forename: Óttar
authors.initials: Ó
authors.lastname: Rolfsson
keywords: endothelium; genetics; metabolic modeling; metabolism; metabolomics; personalized/precision medicine