Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305, USA.
Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
Genes (Basel). 2020 Jul 14;11(7):789. doi: 10.3390/genes11070789.
The genetic mechanisms underlying aortic stenosis (AS) and aortic insufficiency (AI) disease progression remain unclear. We hypothesized that normal aortic valves and those with AS or AI all exhibit unique transcriptional profiles. Normal control (NC) aortic valves were collected from non-matched donor hearts that were otherwise acceptable for transplantation ( = 5). Valves with AS or AI ( = 5, each) were collected from patients undergoing surgical aortic valve replacement. High-throughput sequencing of total RNA revealed 6438 differentially expressed genes (DEGs) for AS vs. NC, 4994 DEGs for AI vs. NC, and 2771 DEGs for AS vs. AI. Among 21 DEGs of interest, , , , , , , , , and were upregulated in both AS and AI compared to NC, whereas , , , , and were downregulated in both AS and AI ( < 0.05). , , , , , and were upregulated only in AS, and was downregulated only in AS ( < 0.05). The functional network for AS clustered around ion regulation, immune regulation, and lipid homeostasis, and that for AI clustered around ERK1/2 regulation. Overall, we report transcriptional profiling data for normal human aortic valves from non-matched donor hearts that were acceptable for transplantation and demonstrated that valves with AS and AI possess unique genetic signatures. These data create a roadmap for the development of novel therapeutics to treat AS and AI.
主动脉瓣狭窄 (AS) 和主动脉瓣关闭不全 (AI) 疾病进展的遗传机制尚不清楚。我们假设正常的主动脉瓣和有 AS 或 AI 的主动脉瓣都具有独特的转录谱。从非匹配供体心脏中收集正常对照 (NC) 主动脉瓣，这些心脏 otherwise acceptable for transplantation ( = 5)。从接受外科主动脉瓣置换术的患者中收集有 AS 或 AI 的瓣膜 ( = 5，各)。对总 RNA 的高通量测序显示，AS 与 NC 相比有 6438 个差异表达基因 (DEGs)，AI 与 NC 相比有 4994 个 DEGs，AS 与 AI 相比有 2771 个 DEGs。在 21 个感兴趣的 DEGs 中， 、 、 、 、 、 、 、 和 在 AS 和 AI 中均高于 NC，而 、 、 、 和 在 AS 和 AI 中均低于 NC ( < 0.05)。 、 、 、 、 和 仅在 AS 中上调，而 仅在 AS 中下调 ( < 0.05)。AS 的功能网络聚集在离子调节、免疫调节和脂质稳态周围，AI 的功能网络聚集在 ERK1/2 调节周围。总的来说，我们报告了来自可接受移植的非匹配供体心脏的正常人类主动脉瓣的转录谱数据，并表明有 AS 和 AI 的瓣膜具有独特的遗传特征。这些数据为开发治疗 AS 和 AI 的新型疗法提供了路线图。
