保留射血分数伴甲状腺功能障碍的老年性心力衰竭的非编码和编码机制。

IF 3.3 3区 医学 Q2 CELL BIOLOGY
Sankalpa Chakraborty, Olivia Sloan, Bryce Dickerson, Gourav Chakraborty, Shuang Li, Curren Bounds, Sophia Lemus, Caleb Hickman, J Mauro Calabrese, Viswanathan Rajagopalan
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引用次数: 0

摘要

心力衰竭伴保留射血分数(HFpEF)是一种致死性、异质性的老年综合征。长链非编码rna (lncrna)构成了大多数功能性哺乳动物转录组,是复杂病理生理的关键调控因子。然而,lncrna在与甲状腺激素(TH)功能障碍相关的HFpEF衰老中的作用尚不清楚。我们研究了早期、重度、老年HFpEF(5、13和20个月)中建立的ZSF1模型。HFpEF组两组血清三萜类化合物在时间上均显著降低。超声心动图显示心脏功能完好。形态学和组织学分析显示HFpEF患者心肌明显肥厚。LncRNA芯片和RT-qPCR显示,3种LncRNA在13月龄HFpEF中显著升高。LncRNA敲低可改善细胞活力,T3(活性TH)可进一步增强细胞活力。微阵列分析显示,两种mrna在早期HFpEF中显著改变。我们还在早期和晚期HFpEF中发现了以前未报道的组织和血清炎症细胞因子标志物。总之,我们在早期和/或晚期甲状腺功能减退HFpEF中发现了新的非编码和编码标记。进一步的研究可能会开发出可翻译的HFpEF诊断和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Noncoding and coding mechanisms of aging heart failure with preserved ejection fraction with thyroid dysfunction.

Heart Failure with preserved Ejection Fraction (HFpEF) is a lethal, heterogeneous, geriatric syndrome. Long noncoding RNAs (lncRNAs) constitute the majority of the functional mammalian transcriptome and are key regulators in complex pathophysiology. However, the roles of lncRNAs in aging HFpEF associated with thyroid hormone (TH) dysfunction are unclear. We investigated the well-established ZSF1 model in early and severe, aged HFpEF (5-, 13-, and 20-months [mo]). Both serum THs significantly decreased in HFpEF in a temporal manner. Echocardiogram showed preserved cardiac function. Morphometric and histologic analyses showed significant cardiac hypertrophy in HFpEF. LncRNA microarray and RT-qPCR revealed that three lncRNAs were significantly increased predominantly in 13-mo HFpEF. LncRNA knockdown showed improvement in cell viability, which was further enhanced with T3 (active TH). Microarray analyses showed that two mRNAs were significantly altered in early HFpEF. We also identified previously unreported tissue and serum inflammatory cytokine markers in early and late HFpEF. Taken together, we have shown novel noncoding and coding markers in early and/or late-aged hypothyroid HFpEF. Further studies may develop translatable diagnostic and therapeutic targets for HFpEF.

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来源期刊
Disease Models & Mechanisms
Disease Models & Mechanisms 医学-病理学
CiteScore
6.60
自引率
7.00%
发文量
203
审稿时长
6-12 weeks
期刊介绍: Disease Models & Mechanisms (DMM) is an online Open Access journal focusing on the use of model systems to better understand, diagnose and treat human disease.
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