Imperial College London

Emeritus ProfessorJeremyNicholson

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Emeritus Professor of Biological Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 3195j.nicholson Website

 
 
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Assistant

 

Ms Wendy Torto +44 (0)20 7594 3225

 
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Location

 

Office no. 665Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Vorkas:2015:10.1021/pr5009898,
author = {Vorkas, PA and Shalhoub, J and Isaac, G and Want, EJ and Nicholson, JK and Holmes, E and Davies, AH},
doi = {10.1021/pr5009898},
journal = {Journal of Proteome Research},
pages = {1389--1399},
title = {Metabolic Phenotyping of Atherosclerotic Plaques Reveals Latent Associations between Free Cholesterol and Ceramide Metabolism in Atherogenesis.},
url = {http://dx.doi.org/10.1021/pr5009898},
volume = {14},
year = {2015}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Current optimum medical treatments have had limited success in the primary prevention of cardiovascular events, underscoring the need for new pharmaceutical targets and enhanced understanding of mechanistic metabolic dysregulation. Here, we use a combination of novel metabolic profiling methodologies, based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) followed by chemometric modeling, data integration, and pathway mapping, to create a systems-level metabolic atlas of atherogenesis. We apply this workflow to compare arterial tissue incorporating plaque lesions to intimal thickening tissue (immediate preplaque stage). We find changes in several metabolite species consistent with well-established pathways in atherosclerosis, such as the cholesterol, purine, pyrimidine, and ceramide pathways. We then illustrate differential levels of previously unassociated lipids to atherogenesis, namely, phosphatidylethanolamine-ceramides (t-test p-values: 3.8 × 10(-6) to 9.8 × 10(-12)). Most importantly, these molecules appear to be interfacing two pathways recognized for their involvement in atherosclerosis: ceramide and cholesterol. Furthermore, we show that β-oxidation intermediates (i.e., acylcarnitines) manifest a pattern indicating truncation of the process and overall dysregulation of fatty acid metabolism and mitochondrial dysfunction. We develop a metabolic framework that offers the ability to map significant statistical associations between detected biomarkers. These dysregulated molecules and consequent pathway modulations may provide novel targets for pharmacotherapeutic intervention.
AU - Vorkas,PA
AU - Shalhoub,J
AU - Isaac,G
AU - Want,EJ
AU - Nicholson,JK
AU - Holmes,E
AU - Davies,AH
DO - 10.1021/pr5009898
EP - 1399
PY - 2015///
SN - 1535-3907
SP - 1389
TI - Metabolic Phenotyping of Atherosclerotic Plaques Reveals Latent Associations between Free Cholesterol and Ceramide Metabolism in Atherogenesis.
T2 - Journal of Proteome Research
UR - http://dx.doi.org/10.1021/pr5009898
UR - http://hdl.handle.net/10044/1/19976
VL - 14
ER -