Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice.
Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice.
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DOI：
10.1371/journal.pone.0292990
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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阻塞性睡眠呼吸暂停（OSA）是一种常见的呼吸障碍，影响了相当一部分成年人。除了引起白天过度嗜睡和神经认知效应外，OSA是心血管疾病的独立危险因素;然而，其潜在机制尚未完全了解。使用暴露于间歇性缺氧（IH）模拟OSA，我们最近报道，暴露于IH的小鼠表现出内皮细胞（EC）激活，这是心血管疾病发展之前的早期过程。虽然IH模型被广泛使用，但它有几个局限性，例如缺氧的严重程度，这在大多数OSA患者中不会发生。最近的研究报道，血红素加氧酶2（Hmox 2-/-）缺失的小鼠在睡眠期间表现出自发性呼吸暂停和升高的儿茶酚胺水平，血红素加氧酶2在颈动脉体中的氧感中起关键作用。在这里，使用RNA测序，我们研究了主动脉EC和心脏组织中的转录组学变化，以了解Hmox 2-/-小鼠中发生的变化。此外，我们通过超声心动图和心电图评估了这些小鼠的心脏结构、功能和电特性。我们发现，Hmox 2-/-小鼠表现出主动脉EC激活。主动脉内皮细胞的转录组学分析显示，差异表达的基因丰富的血液凝固，细胞粘附，细胞呼吸和心肌发育和收缩。类似地，心脏组织中的转录组学分析显示了在线粒体翻译、氧化磷酸化和心肌发育中富集的差异表达基因集。对主动脉内皮细胞和心脏组织的转录组数据分析表明，Hmox 2基因的缺失可能在主动脉内皮细胞和心脏组织上具有共同的细胞网络足迹。超声心动图评价显示，与Hmox 2 +/+小鼠相比，Hmox 2-/-小鼠发生进行性扩张型心肌病和传导异常。总之，我们发现自发发展呼吸暂停的Hmox 2-/-小鼠表现出与心力衰竭一致的EC活化和转录组学和功能变化。
Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease. Although widely used, IH models have several limitations such as the severity of hypoxia, which does not occur in most patients with OSA. Recent studies reported that mice with deletion of hemeoxygenase 2 (Hmox2-/-), which plays a key role in oxygen sensing in the carotid body, exhibit spontaneous apneas during sleep and elevated levels of catecholamines. Here, using RNA-sequencing we investigated the transcriptomic changes in aortic ECs and heart tissue to understand the changes that occur in Hmox2-/- mice. In addition, we evaluated cardiac structure, function, and electrical properties by using echocardiogram and electrocardiogram in these mice. We found that Hmox2-/- mice exhibited aortic EC activation. Transcriptomic analysis in aortic ECs showed differentially expressed genes enriched in blood coagulation, cell adhesion, cellular respiration and cardiac muscle development and contraction. Similarly, transcriptomic analysis in heart tissue showed a differentially expressed gene set enriched in mitochondrial translation, oxidative phosphorylation and cardiac muscle development. Analysis of transcriptomic data from aortic ECs and heart tissue showed loss of Hmox2 gene might have common cellular network footprints on aortic endothelial cells and heart tissue. Echocardiographic evaluation showed that Hmox2-/- mice develop progressive dilated cardiomyopathy and conduction abnormalities compared to Hmox2+/+ mice. In conclusion, we found that Hmox2-/- mice, which spontaneously develop apneas exhibit EC activation and transcriptomic and functional changes consistent with heart failure.
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影响因子：
4
作者：
Cetin-Atalay R;Meliton AY;Wu D;Woods PS;Sun KA;Peng YJ;Nanduri J;Su X;Fang Y;Hamanaka RB;Prabhakar N;Mutlu GM
通讯作者：
Mutlu GM
DOI：
10.1017/gheg.2018.9
发表时间：
2018
期刊：
Global health, epidemiology and genomics
影响因子：
--
作者：
Ruel G;Martin SA;Lévesque JF;Wittert GA;Adams RJ;Appleton SL;Shi Z;Taylor AW
通讯作者：
Taylor AW
影响因子：
76.2
作者：
Benjafield, Adam V.;Ayas, Najib T.;Malhotra, Atul
通讯作者：
Malhotra, Atul
影响因子：
3.4
作者：
Gabryelska A;Łukasik ZM;Makowska JS;Białasiewicz P
通讯作者：
Białasiewicz P
DOI：
10.1164/rccm.201012-2033oc
发表时间：
2011-09-15
影响因子：
24.7
作者：
Arnaud, Claire;Beguin, Pauline C.;Dematteis, Maurice
通讯作者：
Dematteis, Maurice