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  • 标题:Screening for potential targets to reduce stenosis in bioprosthetic heart valves
  • 本地全文:下载
  • 作者:Rudi Foth ; Orr Shomroni ; Matthias Sigler
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2021
  • 卷号:11
  • 期号:1
  • 页码:2464
  • DOI:10.1038/s41598-021-81340-2
  • 出版社:Springer Nature
  • 摘要:Abstract Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduits, we dissected the thickened conduit wall and the thin leaflet to determine gene expression-profiles using ultra deep sequencing. Differential gene expression between pannus and leaflet provided the dataset that was screened for potential targets. Promising target candidates were immunohistologically stained to see protein abundance and the expressing cell type(s). While immunostainings for DDR2 and FGFR2 remained inconclusive, EGFR, ErbB4 and FLT4 were specifically expressed in a subset of tissue macrophages, a cell type known to regulate the initiation, maintenance, and resolution of tissue repair. Taken toghether, our data suggest EGFR, ErbB4 and FLT4 as potential target candidates to limit pannus formation in bioprosthestic replacement valves.
  • 其他摘要:Abstract Progressive stenosis is one of the main factors that limit the lifetime of bioprosthetic valved conduits. To improve long-term performance we aimed to identify targets that inhibit pannus formation on conduit walls. From 11 explanted, obstructed, RNAlater presevered pulmonary valved conduits, we dissected the thickened conduit wall and the thin leaflet to determine gene expression-profiles using ultra deep sequencing. Differential gene expression between pannus and leaflet provided the dataset that was screened for potential targets. Promising target candidates were immunohistologically stained to see protein abundance and the expressing cell type(s). While immunostainings for DDR2 and FGFR2 remained inconclusive, EGFR, ErbB4 and FLT4 were specifically expressed in a subset of tissue macrophages, a cell type known to regulate the initiation, maintenance, and resolution of tissue repair. Taken toghether, our data suggest EGFR, ErbB4 and FLT4 as potential target candidates to limit pannus formation in bioprosthestic replacement valves.
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