RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing
RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing
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DOI：
10.1152/physiolgenomics.00041.2016
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发表时间：
2016-10-01
影响因子：
4.6
通讯作者：
Bosse, Yohan
中科院分区：
文献类型：
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作者：
Guauque-Olarte, Sandra;Droit, Arnaud;Bosse, Yohan
在二尖瓣患者中，导致主动脉瓣狭窄(AS)的分子机制尚不清楚。本研究的目的是利用RNA测序技术(RNA-Seq)鉴定钙化二尖瓣(BAVc)和有(TAVc)和无(TAVn)的三尖瓣之间的差异表达基因。我们收集了10例人类BAVc和9例TAVc，分别来自接受初次主动脉瓣置换术的男性。8个TAVN取自接受心脏移植的男性。用RNA-Seq法检测各瓣膜组织中的mRNA水平，并进行比较。与TAVc相比，BAVc中有两个基因表达上调，没有一个基因表达下调，这表明在二尖瓣和三尖瓣患者中对AS的基因表达反应相似。与TAVn相比，BAVc有462个基因表达上调，282个基因表达下调。与TAVn相比，TAVc有329个基因上调，170个基因下调。在BAVc与TAVn和TAVc与TAVn之间共有273个上调基因和147个下调基因发生了一致的改变，分别占第一次和第二次比较中显著基因的56%和84%。这表明在BAVc中，额外的基因和途径发生了改变。钙化(BAVc和TAVc)和正常(TAVn)主动脉瓣之间的共同通路在BAVc中也发生了更广泛的变化。与正常瓣膜相比，钙化瓣膜中差异表达基因丰富的最高途径是纤维化，这支持重构过程作为治疗靶点。这些发现有助于了解二尖瓣和三尖瓣患者AS的分子基础。
The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up-and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.