Limits...
Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.

McGarrity S, Halldórsson H, Palsson S, Johansson PI, Rolfsson Ó - Front Cardiovasc Med (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, University of Iceland , Reykjavik , Iceland.

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.

No MeSH data available.


Related in: MedlinePlus

Endothelial metabolism and its links to cellular damage, function, and proliferation control. Metabolism, including glycolysis, pentose phosphate pathway, TCA cycle, fatty acid oxidation, and nitric oxide synthase are represented in red. Useful products of metabolism, NO, ATP, and Ca2+ signaling are shown in green. Damaging side products of metabolism are shown in yellow.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4834436&req=5

Figure 1: Endothelial metabolism and its links to cellular damage, function, and proliferation control. Metabolism, including glycolysis, pentose phosphate pathway, TCA cycle, fatty acid oxidation, and nitric oxide synthase are represented in red. Useful products of metabolism, NO, ATP, and Ca2+ signaling are shown in green. Damaging side products of metabolism are shown in yellow.

Mentions: Endothelial cell metabolism has been investigated in multiple contexts including angiogenesis, hypoxia, shear stress, glycemia, and response to perturbations with mediators of vascular health including thrombin, sphingosine-1-phosphate, and more (14–19). The endothelium operates with variable nutrient availability and oxygen partial pressures in a manner that is EC subtype specific (20) and results in altered synergy in the oxidation of its core nutrients glucose, fatty acids, and amino acids (17, 21–23) that are reviewed specifically elsewhere (24, 25) but considered collectively here and illustrated in Figure 1.


Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.

McGarrity S, Halldórsson H, Palsson S, Johansson PI, Rolfsson Ó - Front Cardiovasc Med (2016)

Endothelial metabolism and its links to cellular damage, function, and proliferation control. Metabolism, including glycolysis, pentose phosphate pathway, TCA cycle, fatty acid oxidation, and nitric oxide synthase are represented in red. Useful products of metabolism, NO, ATP, and Ca2+ signaling are shown in green. Damaging side products of metabolism are shown in yellow.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834436&req=5

Figure 1: Endothelial metabolism and its links to cellular damage, function, and proliferation control. Metabolism, including glycolysis, pentose phosphate pathway, TCA cycle, fatty acid oxidation, and nitric oxide synthase are represented in red. Useful products of metabolism, NO, ATP, and Ca2+ signaling are shown in green. Damaging side products of metabolism are shown in yellow.
Mentions: Endothelial cell metabolism has been investigated in multiple contexts including angiogenesis, hypoxia, shear stress, glycemia, and response to perturbations with mediators of vascular health including thrombin, sphingosine-1-phosphate, and more (14–19). The endothelium operates with variable nutrient availability and oxygen partial pressures in a manner that is EC subtype specific (20) and results in altered synergy in the oxidation of its core nutrients glucose, fatty acids, and amino acids (17, 21–23) that are reviewed specifically elsewhere (24, 25) but considered collectively here and illustrated in Figure 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology, University of Iceland , Reykjavik , Iceland.

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.

No MeSH data available.


Related in: MedlinePlus