Article (Scientific journals)
High-density lipoprotein proteome dynamics in human endotoxemia.
Levels, Johannes Hm; Geurts, Pierre; Karlsson, Helen et al.
2011In Proteome Science, 9 (1), p. 34
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Abstract :
[en] BACKGROUND: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L) were challenged with endotoxin (LPS) intravenously (1 ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. RESULTS: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value < 0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants. CONCLUSIONS: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.
Research center :
Giga-Systems Biology and Chemical Biology - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Levels, Johannes Hm;  University of Amsterdam > Department of Experimental Vascular Medicine
Geurts, Pierre ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation
Karlsson, Helen;  Linköping University > Department of Clinical and Experimental Medicine
Marée, Raphaël  ;  Université de Liège - ULiège > GIGA-Management : Plateforme bioinformatique
Ljunggren, Stefan;  Linköping University > Department of Clinical and Experimental Medicine
Fornander, Louise;  Linköping University > Department of Clinical and Experimental Medicine
Wehenkel, Louis  ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation
Lindahl, Mats;  Linköping University > Department of Clinical and Experimental Medicine
Stroes, Erik Sg;  University of Amsterdam > Department of Vascular Medicine,
Kuivenhoven, Jan A;  University of Amsterdam > Department of Vascular Medicine
Meijers, Joost Cm;  University of Amsterdam > Department of Vascular Medicine
Language :
English
Title :
High-density lipoprotein proteome dynamics in human endotoxemia.
Publication date :
28 June 2011
Journal title :
Proteome Science
eISSN :
1477-5956
Publisher :
BioMed Central, United Kingdom
Volume :
9
Issue :
1
Pages :
34
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FEDER - Fonds Européen de Développement Régional [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 18 August 2011

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