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WebPage:
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         headline:Fibroblast polarization over the myocardial infarction time continuum shifts roles from inflammation to angiogenesis
         description:Cardiac fibroblasts are the major producers of extracellular matrix (ECM) to form infarct scar. We hypothesized that fibroblasts undergo a spectrum of phenotype states over the course of myocardial infarction (MI) from early onset to scar formation. Fibroblasts were isolated from the infarct region of C57BL/6J male mice (3–6 months old, n = 60) at days 0 (no MI control) and 1, 3, or 7 after MI. Whole transcriptome analysis was performed by RNA-sequencing. Of the genes sequenced, 3371 were differentially expressed after MI. Enrichment analysis revealed that MI day 1 fibroblasts displayed pro-inflammatory, leukocyte-recruiting, pro-survival, and anti-migratory phenotype through Tnfrsf9 and CD137 signaling. MI day 3 fibroblasts had a proliferative, pro-fibrotic, and pro-angiogenic profile with elevated Il4ra signaling. MI day 7 fibroblasts showed an anti-angiogenic homeostatic-like myofibroblast profile and with a step-wise increase in Acta2 expression. MI day 7 fibroblasts relied on Pik3r3 signaling to mediate Tgfb1 effects and Fgfr2 to regulate PI3K signaling. In vitro, the day 3 MI fibroblast secretome stimulated angiogenesis, while day 7 MI fibroblast secretome repressed angiogenesis through Thbs1 signaling. Our results reveal novel mechanisms for fibroblasts in expressing pro-inflammatory molecules and regulating angiogenesis following MI.
         datePublished:2019-01-11T00:00:00Z
         dateModified:2019-01-11T00:00:00Z
         pageStart:1
         pageEnd:16
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         sameAs:https://doi.org/10.1007/s00395-019-0715-4
         keywords:
            Myocardial infarction
            Cardiac remodeling
            Fibroblast
            Transcriptome
            Angiogenesis
            Extracellular matrix
            Cardiology
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      headline:Fibroblast polarization over the myocardial infarction time continuum shifts roles from inflammation to angiogenesis
      description:Cardiac fibroblasts are the major producers of extracellular matrix (ECM) to form infarct scar. We hypothesized that fibroblasts undergo a spectrum of phenotype states over the course of myocardial infarction (MI) from early onset to scar formation. Fibroblasts were isolated from the infarct region of C57BL/6J male mice (3–6 months old, n = 60) at days 0 (no MI control) and 1, 3, or 7 after MI. Whole transcriptome analysis was performed by RNA-sequencing. Of the genes sequenced, 3371 were differentially expressed after MI. Enrichment analysis revealed that MI day 1 fibroblasts displayed pro-inflammatory, leukocyte-recruiting, pro-survival, and anti-migratory phenotype through Tnfrsf9 and CD137 signaling. MI day 3 fibroblasts had a proliferative, pro-fibrotic, and pro-angiogenic profile with elevated Il4ra signaling. MI day 7 fibroblasts showed an anti-angiogenic homeostatic-like myofibroblast profile and with a step-wise increase in Acta2 expression. MI day 7 fibroblasts relied on Pik3r3 signaling to mediate Tgfb1 effects and Fgfr2 to regulate PI3K signaling. In vitro, the day 3 MI fibroblast secretome stimulated angiogenesis, while day 7 MI fibroblast secretome repressed angiogenesis through Thbs1 signaling. Our results reveal novel mechanisms for fibroblasts in expressing pro-inflammatory molecules and regulating angiogenesis following MI.
      datePublished:2019-01-11T00:00:00Z
      dateModified:2019-01-11T00:00:00Z
      pageStart:1
      pageEnd:16
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1007/s00395-019-0715-4
      keywords:
         Myocardial infarction
         Cardiac remodeling
         Fibroblast
         Transcriptome
         Angiogenesis
         Extracellular matrix
         Cardiology
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      name:Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, USA
      name:Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, USA
      name:Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, USA
      name:The Roslin Institute, University of Edinburgh, Midlothian, UK
      name:Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, USA
      name:Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, USA
      name:Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, USA
      name:Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, USA
      name:Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, USA

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