Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Demetz, E; Schroll, A; Auer, K; Heim, C; Patsch, JR; Eller, P; Theurl, M; Theurl, I; Theurl, M; Seifert, M; Lener, D; Stanzl, U; Haschka, D; Asshoff, M; Dichtl, S; Nairz, M; Huber, E; Stadlinger, M; Moschen, AR; Li, X; Pallweber, P; Scharnagl, H; Stojakovic, T; März, W; Kleber, ME; Garlaschelli, K; Uboldi, P; Catapano, AL; Stellaard, F; Rudling, M; Kuba, K; Imai, Y; Arita, M; Schuetz, JD; Pramstaller, PP; Tietge, UJF; Trauner, M; Norata, GD; Claudel, T; Hicks, AA; Weiss, G; Tancevski, I.
The arachidonic acid metabolome serves as a conserved regulator of cholesterol metabolism.
Cell Metab. 2014; 20(5):787-798 Doi: 10.1016/j.cmet.2014.09.004 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Claudel Thierry; Eller Philipp; März Winfried; Scharnagl Hubert; Stojakovic Tatjana; Trauner Michael
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Abstract:: Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By combining data from a GWAS screening in >100,000 individuals of European ancestry, mediator lipidomics, and functional validation studies in mice, we identify the AA metabolome as an important regulator of cholesterol homeostasis. Pharmacological modulation of AA metabolism by aspirin induced hepatic generation of leukotrienes (LTs) and lipoxins (LXs), thereby increasing hepatic expression of the bile salt export pump Abcb11. Induction of Abcb11 translated in enhanced reverse cholesterol transport, one key function of HDL. Further characterization of the bioactive AA-derivatives identified LX mimetics to lower plasma LDL-C. Our results define the AA metabolomeasconserved regulator of cholesterol metabolism, and identify AA derivatives as promising therapeutics to treat cardiovascular disease in humans.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Arachidonate 5-Lipoxygenase - metabolism; Arachidonic Acid - metabolism; Aspirin - therapeutic use; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Bile Acids and Salts - metabolism; Cells, Cultured -; Cholesterol - blood; Cholesterol - metabolism; Cholesterol, HDL - blood; Cholesterol, HDL - metabolism; Humans -; Leukotrienes - metabolism; Liver - drug effects; Liver - metabolism; Metabolome -; Mice -; Mice, Inbred C57BL -