title: Lipid regulators during atherogenesis: expression of LXR, PPAR, and SREBP mRNA in the human aorta.
abstract: Transcription factors LXRs, PPARs, and SREBPs have been implicated in a multitude of physiological and pathological processes including atherogenesis. However, little is known about the regulation of these transcription factors at different stages of atherosclerosis progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to compare the contents of mRNAs in pairs intact-injured aorta fragments taken from the same donors. Only minor changes in LXRα, LXRβ, PPARα, PPARγ, SREBP1, and SREBP2 mRNA levels were found in initial lesions as compared with intact non-diseased tissue. The contents of all mRNAs but SREBP2 mRNA were found to be progressively up-regulated in fatty streaks and fibrous lipoid plaques. These changes were only partially reproduced in cultured macrophages upon lipid loading. Wave-shaped changes in abundance of correlations between given group of mRNAs and 28 atherosclerosis-related mRNA species in the course of atherogenesis were observed. The impact of specific mRNA correlations on the total correlations also significantly varied between different lesion types. The study suggests that the extent and forms of LXR/PPAR/SREBP participation in intima functions vary nonlinear in individual fashion in atherogenesis. We speculate that the observed changes in mRNAs expression and coupling reflect shifts in lipid ligands availability and cellular composition in the course of atherosclerosis progression.
authors.affiliation: Biological Faculty, Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Shchelkunova
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Morozov
authors.forename: Petr M
authors.initials: PM
authors.lastname: Rubtsov
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sobenin
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
authors.forename: Irina V
authors.initials: IV
authors.lastname: Andrianova
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Smirnov
mesh_terms: D000328:Adult; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D047495:PPAR gamma; D012333:RNA, Messenger; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2