High Density Lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudy

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dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.authorYetukuri, Laxmanen_US
dc.contributor.authorHuopaniemi, Ilkkaen_US
dc.contributor.authorKoivuniemi, Artturien_US
dc.contributor.authorMaranghi, Mariannaen_US
dc.contributor.authorHiukka, Anneen_US
dc.contributor.authorNygren, Helien_US
dc.contributor.authorKaski, Samuelen_US
dc.contributor.authorTaskinen, Marja-Riittaen_US
dc.contributor.authorVattulainen, Ilpoen_US
dc.contributor.authorJauhiainen, Mattien_US
dc.contributor.authorOresic, Matejen_US
dc.contributor.departmentHelsinki Insititute for Information Technology HIITen
dc.contributor.departmentTietojenkäsittelytieteen laitoen
dc.contributor.departmentDepartment of Applied Physicsen
dc.date.accessioned2017-05-11T08:40:16Z
dc.date.available2017-05-11T08:40:16Z
dc.date.issued2011en_US
dc.descriptionVK: airc hiit
dc.description.abstractIn a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associated with fenofibrate treatment and the drug-induced Hcy levels in the FIELD substudy. We found that fenofibrate leads to complex HDL compositional changes including increased apoA-II, diminishment of lysophosphatidylcholines and increase of sphingomyelins. Ethanolamine plasmalogens were diminished only in a subgroup of fenofibrate-treated patients with elevated homocysteine levels. Finally we performed molecular dynamics simulations to qualitatively reconstitute HDL particles in silico. We found that increased number of apoA-II excludes neutral lipids from HDL surface and apoA-II is more deeply buried in the lipid matrix than apoA-I. In conclusion, a detailed molecular characterization of HDL may provide surrogates for predictors of drug response and thus help identify the patients who might benefit from fenofibrate treatment.en
dc.description.versionPeer revieweden
dc.format.extent1-12
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationYetukuri, L, Huopaniemi, I, Koivuniemi, A, Maranghi, M, Hiukka, A, Nygren, H, Kaski, S, Taskinen, M-R, Vattulainen, I, Jauhiainen, M & Oresic, M 2011, ' High Density Lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudy ', PloS one, vol. 6, no. 8, e23589, pp. 1-12 . https://doi.org/10.1371/journal.pone.0023589en
dc.identifier.doi10.1371/journal.pone.0023589en_US
dc.identifier.issn1932-6203
dc.identifier.otherPURE UUID: 95e12de5-b27b-4ca2-a60e-65416a19ea57en_US
dc.identifier.otherPURE ITEMURL: https://research.aalto.fi/en/publications/95e12de5-b27b-4ca2-a60e-65416a19ea57en_US
dc.identifier.otherPURE LINK: http://dx.plos.org/10.1371/journal.pone.0023589en_US
dc.identifier.otherPURE FILEURL: https://research.aalto.fi/files/12866971/journal.pone.0023589.pdfen_US
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/25708
dc.identifier.urnURN:NBN:fi:aalto-201705114092
dc.language.isoenen
dc.relation.ispartofseriesPLOS ONEen
dc.relation.ispartofseriesVolume 6, issue 8en
dc.rightsopenAccessen
dc.titleHigh Density Lipoprotein structural changes and drug response in lipidomic profiles following the long-term fenofibrate therapy in the FIELD substudyen
dc.typeA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessäfi
dc.type.versionpublishedVersion
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