The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.
The long non-coding HOTAIR is modulated by cyclic stretch and WNT/β-CATENIN in human aortic valve cells and is a novel repressor of calcification genes.
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DOI：
10.1371/journal.pone.0096577
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nigam V
中科院分区：
文献类型：
--
作者：
Carrion K;Dyo J;Patel V;Sasik R;Mohamed SA;Hardiman G;Nigam V
主动脉瓣钙化是一个重大而严重的临床问题，目前尚无有效的药物治疗方法。出生时患有二尖瓣主动脉瓣的人（占人口的 1-2%）发生主动脉瓣钙化的风险最高。主动脉瓣钙化涉及钙化和炎症基因表达的增加。与正常三尖瓣主动脉瓣相比，二尖瓣主动脉瓣叶的生物力学应变增加。 BAV 钙化的分子发病机制尚不清楚，尤其是对机械拉伸的分子反应。 HOTAIR 是一种长链非编码 RNA (lncRNA)，与癌症有关，但尚未在心脏病中进行研究。我们发现，在暴露于循环拉伸的 BAV 和人主动脉间质细胞 (AVIC) 中，HOTAIR 水平降低。在 AVIC 中通过 siRNA 降低 HOTAIR 水平会导致钙化基因表达增加。我们的数据表明 β-CATENIN 是一种抑制 HOTAIR 的拉伸响应信号通路。这是第一份证明 HOTAIR 具有机械反应性并受到 WNT β-CATENIN 信号传导抑制的报告。这些发现提供了 HOTAIR 参与主动脉瓣钙化的新证据。
Aortic valve calcification is a significant and serious clinical problem for which there are no effective medical treatments. Individuals born with bicuspid aortic valves, 1–2% of the population, are at the highest risk of developing aortic valve calcification. Aortic valve calcification involves increased expression of calcification and inflammatory genes. Bicuspid aortic valve leaflets experience increased biomechanical strain as compared to normal tricuspid aortic valves. The molecular pathogenesis involved in the calcification of BAVs are not well understood, especially the molecular response to mechanical stretch. HOTAIR is a long non-coding RNA (lncRNA) that has been implicated with cancer but has not been studied in cardiac disease. We have found that HOTAIR levels are decreased in BAVs and in human aortic interstitial cells (AVICs) exposed to cyclic stretch. Reducing HOTAIR levels via siRNA in AVICs results in increased expression of calcification genes. Our data suggest that β-CATENIN is a stretch responsive signaling pathway that represses HOTAIR. This is the first report demonstrating that HOTAIR is mechanoresponsive and repressed by WNT β-CATENIN signaling. These findings provide novel evidence that HOTAIR is involved in aortic valve calcification.
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影响因子：
64.8
作者：
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影响因子：
5.3
作者：
Kaden, JJ;Dempfle, CE;Borggrefe, M
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影响因子：
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影响因子：
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通讯作者：
Nurminskaya, Maria
影响因子：
3.7
作者：
Edep, ME;Shirani, J;Brown, DL
通讯作者：
Brown, DL