High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice.
High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice.
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DOI：
10.3390/ijms19020533
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发表时间：
2018-02-10
影响因子：
5.6
通讯作者：
Donoso P
中科院分区：
文献类型：
--
作者：
Sánchez G;Araneda F;Peña JP;Finkelstein JP;Riquelme JA;Montecinos L;Barrientos G;Llanos P;Pedrozo Z;Said M;Bull R;Donoso P
室性心律失常是心源性猝死的常见原因，在肥胖者中发生率较高。肌浆网钙释放通道兰尼定受体(RyR2)的异常门控可导致室性心律失常。由于肥胖会促进氧化应激，而RyR2是氧化还原敏感的通道，我们调查了肥胖小鼠的RyR2活性是否发生了变化。喂食高脂饮食(HFD)的小鼠在8周后变得肥胖，室性心律失常的发生率显着增加。从肥胖小鼠心脏分离的单个RyR2通道在平面双层膜上比从对照小鼠心脏分离的通道更活跃。在分子水平上，来自HFD喂养的小鼠的RyR2通道的游离硫醇残基大大减少，这表明氧化还原修饰是导致更高活性的原因。饮用水中提供的载脂蛋白可完全阻止高脂饲料喂养的小鼠出现室性心律失常，并使蛋白质中游离硫醇残基的活性和含量正常化。HFD增加心脏中NOX4的表达，NOX4是NADPH氧化酶的一个亚型。我们的结果表明，HFD通过氧化还原依赖的机制增加RyR2通道的活性，有利于室性心律失常的出现。
Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.
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DOI：
10.1136/heartjnl-2014-306238
发表时间：
2015-02
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Adabag S;Huxley RR;Lopez FL;Chen LY;Sotoodehnia N;Siscovick D;Deo R;Konety S;Alonso A;Folsom AR
通讯作者：
Folsom AR
DOI：
10.1152/ajpendo.00398.2012
发表时间：
2013-02-01
影响因子：
5.1
作者：
Pepping, Jennifer K.;Freeman, Linnea R.;Bruce-Keller, Annadora J.
通讯作者：
Bruce-Keller, Annadora J.
影响因子：
64.5
作者：
Marx, SO;Reiken, S;Marks, AR
通讯作者：
Marks, AR
影响因子：
9.8
作者：
Ikemoto, S;Takahashi, M;Ezaki, O
通讯作者：
Ezaki, O
影响因子：
5.4
作者：
Narayanan, Kumar;Zhang, Lin;Chugh, Sumeet S.
通讯作者：
Chugh, Sumeet S.