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

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

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 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Claudel Thierry
Eller Philipp
Maerz Winfried
Scharnagl Hubert
Stojakovic Tatjana
Trauner Michael
Altmetrics:

Dimensions Citations:

Plum Analytics:
Number of Figures: 8
| | | | | | | |
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 -

© Meduni Graz Impressum