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Alterations in high-density lipoprotein proteome and function associated with persistent organic pollutants
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
Swedish Toxicol Science Research Centre, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
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2017 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 98, p. 204-211Article in journal (Refereed) Published
Abstract [en]

There is a growing body of evidence that persistent organic pollutants (POPs) may increase the risk for cardiovascular disease (CVD), but the mechanisms remain unclear. High- density lipoprotein (HDL) acts protective against CVD by different processes, andwe have earlier found that HDL from subjects with CVD contains higher levels of POPs than healthy controls. In the present study, we have expanded analyses on the same individuals living in a contaminated community and investigated the relationship between the HDL POP levels and protein composition/ function. HDL from17 subjectswas isolated by ultracentrifugation. HDL protein composition, using nanoliquid chromatography tandemmass spectrometry, and antioxidant activity were analyzed. The associations of 16 POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, with HDL proteins/functionswere investigated by partial least square and multiple linear regression analysis. Proteomic analyses identified 118 HDL proteins, of which ten were significantly (p b 0.05) and positively associated with the combined level of POPs or with highly chlorinated PCB congeners. Among these, cholesteryl ester transfer protein and phospholipid transfer protein, as well as the inflammatory marker serum amyloid A, were found. The serum paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway analysis demonstrated that up- regulated proteinswere associatedwith biological processes involving lipoproteinmetabolism, while down- regulated proteinswere associatedwith processes such as negative regulation of proteinases, acute phase response, platelet degranulation, and complement activation. These results indicate an association between POP levels, especially highly chlorinated PCBs, and HDL protein alterations that may result in a less functional particle. Further studies are needed to determine causality and the importance of other environmental factors. Nevertheless, this study provides a first insight into a possible link between exposure to POPs and risk of CVD. (C) 2016 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD , 2017. Vol. 98, p. 204-211
Keywords [en]
Cardiovascular disease; Environmental; HDL; Lipoproteins; Persistent organic pollutants
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Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-133725DOI: 10.1016/j.envint.2016.11.008ISI: 000389913500024PubMedID: 27865523OAI: oai:DiVA.org:liu-133725DiVA, id: diva2:1063913
Note

Funding Agencies|Research Council of Southeast Sweden [FORSS-235481, FORSS-387841]

Available from: 2017-01-11 Created: 2017-01-09 Last updated: 2018-01-13

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Ljunggren, StefanHelmfrid, IngelaFredrikson, MatsWingren, GunKarlsson, HelenLindahl, Mats
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Division of Neuro and Inflammation ScienceFaculty of Medicine and Health SciencesOccupational and Environmental Medicine Center
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