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A differential network approach to exploring differences between biological states: an application to prediabetes.

https://arctichealth.org/en/permalink/ahliterature130667
Source
PLoS One. 2011;6(9):e24702
Publication Type
Article
Date
2011
Author
Beatriz Valcárcel
Peter Würtz
Nafisa-Katrin Seich al Basatena
Taru Tukiainen
Antti J Kangas
Pasi Soininen
Marjo-Riitta Järvelin
Mika Ala-Korpela
Timothy M Ebbels
Maria de Iorio
Author Affiliation
Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Source
PLoS One. 2011;6(9):e24702
Date
2011
Language
English
Publication Type
Article
Keywords
Blood Glucose - chemistry
Cohort Studies
Diabetes Mellitus - metabolism
Dyslipidemias - genetics
Female
Finland
Gene Regulatory Networks
Genetic Predisposition to Disease - genetics
Genetic Variation
Humans
Lipoproteins - chemistry
Lipoproteins, HDL - chemistry
Magnetic Resonance Spectroscopy - methods
Male
Models, Biological
Models, Genetic
Models, Statistical
Phenotype
Systems Biology
Abstract
Variations in the pattern of molecular associations are observed during disease development. The comprehensive analysis of molecular association patterns and their changes in relation to different physiological conditions can yield insight into the biological basis of disease-specific phenotype variation.
Here, we introduce a formal statistical method for the differential analysis of molecular associations via network representation. We illustrate our approach with extensive data on lipoprotein subclasses measured by NMR spectroscopy in 4,406 individuals with normal fasting glucose, and 531 subjects with impaired fasting glucose (prediabetes). We estimate the pair-wise association between measures using shrinkage estimates of partial correlations and build the differential network based on this measure of association. We explore the topological properties of the inferred network to gain insight into important metabolic differences between individuals with normal fasting glucose and prediabetes.
Differential networks provide new insights characterizing differences in biological states. Based on conventional statistical methods, few differences in concentration levels of lipoprotein subclasses were found between individuals with normal fasting glucose and individuals with prediabetes. By performing the differential analysis of networks, several characteristic changes in lipoprotein metabolism known to be related to diabetic dyslipidemias were identified. The results demonstrate the applicability of the new approach to identify key molecular changes inaccessible to standard approaches.
Notes
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PubMed ID
21980352 View in PubMed
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Lipoprotein-associated phosphatidylethanol increases the plasma concentration of vascular endothelial growth factor.

https://arctichealth.org/en/permalink/ahliterature9489
Source
Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1037-42
Publication Type
Article
Date
Jun-2004
Author
Marja K Liisanantti
Minna L Hannuksela
Maria E Rämet
Markku J Savolainen
Author Affiliation
Department of Internal Medicine, University of Oulu, Oulu, Finland.
Source
Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1037-42
Date
Jun-2004
Language
English
Publication Type
Article
Keywords
Adult
Alcohol Drinking
Alcoholism - blood
Animals
Arteriosclerosis - prevention & control
Biological Transport - drug effects
Endothelium, Vascular - drug effects - secretion
Ethanol - pharmacology
Humans
Lipoproteins, HDL - chemistry
MAP Kinase Signaling System - drug effects
Male
Middle Aged
Models, Biological
Phosphatidylinositols - pharmacology
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Vascular Endothelial Growth Factor A - blood - secretion
Abstract
OBJECTIVE: To study whether qualitative changes in high-density lipoprotein (HDL) phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis, we investigated whether phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) from endothelial cells. METHODS AND RESULTS: PEth increased the secretion of VEGF into the culture medium of EA.hy 926 endothelial cells. The mitogen-activated protein kinase (MAPK) phosphorylation increased by 3.3-fold and protein kinase C (PKC) by 2.2-fold by PEth-containing HDL. Moreover, we showed that intravenous injection of PEth incorporated into HDL particles increased plasma concentration of VEGF by 2.4-fold in rats in vivo. Similar effect was observed when the rats were injected with HDL particles isolated from alcohol drinkers. CONCLUSIONS: HDL particles containing PEth affect endothelial cells by MAPK and PKC signaling. This may mediate the effects of ethanol on the arterial wall by increasing VEGF secretion from endothelial vascular cells. That may explain, at least in part, the beneficial effect of moderate alcohol consumption on atherosclerosis.
PubMed ID
15087306 View in PubMed
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