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@ARTICLE{Xue:180812,
      author       = {H. Xue and X. Chen$^*$ and C. Yu and Y. Deng and Y. Zhang
                      and S. Chen and X. Chen and K. Chen and Y. Yang and W. Ling},
      title        = {{G}ut {M}icrobially {P}roduced {I}ndole-3-{P}ropionic
                      {A}cid {I}nhibits {A}therosclerosis by {P}romoting {R}everse
                      {C}holesterol {T}ransport and {I}ts {D}eficiency {I}s
                      {C}ausally {R}elated to {A}therosclerotic {C}ardiovascular
                      {D}isease},
      journal      = {Circulation research},
      volume       = {131},
      number       = {5},
      issn         = {0009-7330},
      address      = {New York, NY},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2022-01574},
      pages        = {404-420},
      year         = {2022},
      note         = {#EA:C070# / 2022 Aug 19;131(5):404-420},
      abstract     = {BACKGROUND:Accumulating evidence has shown that disorders
                      in the gut microbiota and derived metabolites affect the
                      development of atherosclerotic cardiovascular disease
                      (ASCVD). However, which and how specific gut microbial
                      metabolites contribute to the progression of atherosclerosis
                      and the clinical relevance of their alterations remain
                      unclear.METHODS:We performed integrated
                      microbiome–metabolome analysis of 30 patients with
                      coronary artery disease (CAD) and 30 age- and sex-matched
                      healthy controls to identify CAD-associated microbial
                      metabolites, which were then assessed in an independent
                      population of patients with ASCVD and controls (n=256). We
                      further investigate the effect of CAD-associated microbial
                      metabolites on atherosclerosis and the mechanisms of the
                      action.RESULTS:Indole-3-propionic acid (IPA), a solely
                      microbially derived tryptophan metabolite, was the most
                      downregulated metabolite in patients with CAD. Circulating
                      IPA was then shown in an independent population to be
                      associated with risk of prevalent ASCVD and correlated with
                      the ASCVD severity. Dietary IPA supplementation alleviates
                      atherosclerotic plaque development in ApoE−/− mice. In
                      murine- and human-derived macrophages, administration of IPA
                      promoted cholesterol efflux from macrophages to ApoA-I
                      through an undescribed miR-142-5p/ABCA1 (ATP-binding
                      cassette transporter A1) signaling pathway. Further in vivo
                      studies demonstrated that IPA facilitates macrophage reverse
                      cholesterol transport, correlating with the regulation of
                      miR-142-5p/ABCA1 pathway, whereas reduced IPA production
                      contributed to the aberrant overexpression of miR-142-5p in
                      macrophages and accelerated the progression of
                      atherosclerosis. Moreover, the miR-142-5p/ABCA1/reverse
                      cholesterol transport axis in macrophages were dysregulated
                      in patients with CAD, and correlated with the changes in
                      circulating IPA levels.CONCLUSIONS:Our study identify a
                      previously unknown link between specific gut
                      microbiota-derived tryptophan metabolite and ASCVD. The
                      microbial metabolite IPA/miR-142-5p/ABCA1 pathway may
                      represent a promising therapeutic target for ASCVD.},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35893593},
      doi          = {10.1161/CIRCRESAHA.122.321253},
      url          = {https://inrepo02.dkfz.de/record/180812},
}