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@ARTICLE{Fraunberger:120524,
      author       = {P. Fraunberger and E. Gröne$^*$ and H.-J. Gröne$^*$ and
                      H. Drexel and A. K. Walli},
      title        = {{E}zetimibe reduces cholesterol content and {NF}-kappa{B}
                      activation in liver but not in intestinal tissue in guinea
                      pigs.},
      journal      = {Journal of Inflammation},
      volume       = {14},
      number       = {1},
      issn         = {1476-9255},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2017-00953},
      pages        = {3},
      year         = {2017},
      abstract     = {Statins (HMG CoA reductase inhibitors), in addition to
                      reducing circulating cholesterol and incidence of coronary
                      heart disease, also have pleiotropic, anti-inflammatory
                      effects. Patients with chronic liver diseases, non-alcoholic
                      fatty liver disease (NAFLD) or hepatitis C are often
                      excluded from statin therapy because of adverse effects in a
                      small cohort of patients despite increased cardiovascular
                      risk cholesterol. Ezetimibe, which inhibits cholesterol
                      absorption by inhibition of Niemann-Pick C1 like 1 (NPC1L1)
                      protein in the brush border of intestinal cells, has been
                      suggested as a new therapeutic option in these
                      patients.Effects of ezetimibe on lipoprotein metabolism,
                      hepatic and intestinal lipid content in guinea pigs, an
                      animal model with a lipoprotein profile and pattern similar
                      to humans were investigated. In order to investigate a
                      possible effect of ezetimibe on cholesterol induced
                      inflammation NF-kappaB activation as an indicator for
                      inflammatory processes in liver and gut tissue was
                      measured.Lipid enriched diet led to accumulation of lipids
                      in hepatic tissue which caused strong hepatic NF-kappaB
                      activation. Ezetimibe reduced lipid diet induced increase of
                      circulating cholesterol by about $77\%$ and prevent hepatic
                      NF-kappaB activation almost completely. In contrast in
                      intestinal cells Ezetimibe, though lowering diet induced
                      cholesterol accumulation, increased triglyceride content and
                      subsequent NF-kappaB activation.In summary these data show,
                      that ezetimibe effectively reduced diet induced circulating
                      cholesterol levels, hepatic lipid accumulation and
                      inflammatory response in our guinea pig model. However this
                      drug elicited a local inflammatory response in intestinal
                      tissue. Whether these diverse effects of ezetimibe on
                      inflammatory parameters such as NF-kappaB have clinical
                      relevance remains to be determined.},
      cin          = {G130},
      ddc          = {610},
      cid          = {I:(DE-He78)G130-20160331},
      pnm          = {322 - Genetics and Pathophysiology (POF3-322)},
      pid          = {G:(DE-HGF)POF3-322},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28167864},
      pmc          = {pmc:PMC5288872},
      doi          = {10.1186/s12950-017-0150-y},
      url          = {https://inrepo02.dkfz.de/record/120524},
}