Pediatric Cardiology and Intensive Care Medicine, Georg-August University Göttingen, Robert-Koch Str. 40, 37075, Göttingen, Germany.
Department of Developmental Biochemistry, DNA Microarray and Deep-Sequencing Facility, Faculty of Medicine, Georg-August University Göttingen, Justus-von-Liebig-Weg 11, 37077, Göttingen, Germany.
Sci Rep. 2021 Jan 28;11(1):2464. doi: 10.1038/s41598-021-81340-2.
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.
进行性狭窄是限制生物瓣管道寿命的主要因素之一。为了改善长期性能，我们旨在确定抑制管道壁上血管翳形成的靶点。我们从 11 个已取出的、阻塞的、使用 RNAlater 保存的肺动脉瓣管道中，解剖了增厚的管道壁和薄的瓣叶，使用超深度测序来确定基因表达谱。血管翳和瓣叶之间的差异基因表达为筛选潜在靶点提供了数据集。有前途的候选靶点通过免疫组织化学染色来观察蛋白质丰度和表达细胞类型。虽然 DDR2 和 FGFR2 的免疫染色结果仍不确定，但 EGFR、ErbB4 和 FLT4 特异性地表达在一组组织巨噬细胞中，这种细胞类型已知可调节组织修复的启动、维持和解决。综上所述，我们的数据表明 EGFR、ErbB4 和 FLT4 是限制生物瓣置换瓣膜中血管翳形成的潜在靶点候选物。
