E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme.
E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme.
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DOI：
10.1016/j.redox.2022.102369
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发表时间：
2022-08
期刊：
影响因子：
11.4
通讯作者：
Gross, Eric R.
中科院分区：
文献类型：
--
作者：
Yu, Xuan;Zeng, Xiaocong;Xiao, Feng;Chen, Ri;Sinharoy, Pritam;Gross, Eric R.
含有包括乙醛在内的醛的电子烟气雾剂由乙醛脱氢酶2(ALDH2)代谢。然而，人们对电子烟中的醛暴露，再加上失活的ALDH2基因变体ALDH2*2(存在于世界8%的人口中)如何影响心血管氧化应激知之甚少。这项研究旨在确定电子烟气雾剂暴露，再加上遗传因素，如何影响野生型ALDH2和ALDH2*2敲入小鼠的心血管氧化应激。使用选择性离子流质谱，我们确定电子烟气雾剂中的乙醛含量比甲醛或丙烯醛高出10倍。基于这一发现，我们测试了分离的ALDH2*2原代心肌细胞对乙醛的反应，以及与野生型ALDH2啮齿动物相比，使用遥测仪检测完整的ALDH2*2敲入啮齿动物对电子烟气溶胶暴露10天的生理和分子水平的反应。与野生型ALDH2心肌细胞相比，乙醛(1μM)可使ALDH2*2分离的心肌细胞峰值钙内流增加4倍，ROS产生增加2倍，4-HNE诱导的蛋白加合物增加2倍。与暴露在空气中的小鼠相比，接触电子烟10天后，ALDH2*2小鼠的心率增加了∼200次/分钟，而ALDH2小鼠的心率增加了∼150次/分钟。暴露于电子烟的气雾剂可使两种品系的∼小鼠的蛋白质羰化、脂质过氧化和核因子-κB的磷酸化水平提高1.3到2倍，这种反应在ALDH2*2小鼠中加剧。我们的发现表明，携带ALDH2*2基因变异的人可能更容易因接触电子烟气雾剂而增加心血管氧化应激。约5.4亿人的乙醛脱氢酶2(ALDH2*2)基因变异限制了乙醛代谢。鲜为人知的是，当电子烟暴露于ALDH2*2变种时，如何影响心血管氧化应激。与野生型相比，ALDH2*2心肌细胞和啮齿类动物在接触乙醛或电子烟后有更高的氧化应激水平。携带ALDH2*2变异的人可能更容易受到电子烟暴露造成的心血管氧化应激的影响。
E-cigarette aerosol containing aldehydes, including acetaldehyde, are metabolized by the enzyme aldehyde dehydrogenase 2 (ALDH2). However, little is known how aldehyde exposure from e-cigarettes, when coupled with an inactivating ALDH2 genetic variant, ALDH2*2 (present in 8% of the world population), affects cardiovascular oxidative stress. The study was to determine how e-cigarette aerosol exposure, coupled with genetics, impacts cardiovascular oxidative stress in wild type ALDH2 and ALDH2*2 knock-in mice. Using selective ion flow mass spectrometry, we determined e-cigarette aerosol contains acetaldehyde levels 10-fold higher than formaldehyde or acrolein. Based on this finding, we tested how isolated ALDH2*2 primary cardiomyocytes respond to acetaldehyde and how intact ALDH2*2 knock-in rodents instrumented with telemeters respond physiologically and at the molecular level to 10 days of e-cigarette aerosol exposure relative to wild type ALDH2 rodents. For ALDH2*2 isolated cardiomyocytes, acetaldehyde (1 μM) caused a 4-fold greater peak calcium influx, 2-fold increase in ROS production and 2-fold increase in 4-HNE-induced protein adducts relative to wild-type ALDH2 cardiomyocytes. The heart rate in ALDH2*2 mice increased ∼200 beats/min, while, heart rate in ALDH2 mice increased ∼150 beats/min after 10 days of e-cigarette exposure, relative to air-exposed mice. E-cigarette aerosol exposure triggered ∼1.3 to 2-fold higher level of protein carbonylation, lipid peroxidation, and phosphorylation of NF-κB for both strains of mice, with this response exacerbated for ALDH2*2 mice. Our findings indicate people carrying an ALDH2*2 genetic variant may be more susceptible to increases in cardiovascular oxidative stress from e-cigarette aerosol exposure. ~540 million people have a genetic variant in aldehyde dehydrogenase 2 (ALDH2*2) that limits aldehyde metabolism. Little is known how e-cigarette exposure, when coupled with the ALDH2*2 variant, impacts cardiovascular oxidative stress. ALDH2*2 cardiomyocytes and rodents vs. wild type have higher oxidative stress levels after aldehyde or e-cigarette exposure. People with an ALDH2*2 variant may be more susceptible to cardiovascular oxidative stress from e-cigarette exposure.
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影响因子：
37.8
作者：
Koda K;Salazar-Rodriguez M;Corti F;Chan NY;Estephan R;Silver RB;Mochly-Rosen D;Levi R
通讯作者：
Levi R
影响因子：
64.5
作者：
Jiang L;Wang M;Lin S;Jian R;Li X;Chan J;Dong G;Fang H;Robinson AE;GTEx Consortium;Snyder MP
通讯作者：
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影响因子：
2.1
作者：
Farsalinos KE;Tsiapras D;Kyrzopoulos S;Savvopoulou M;Voudris V
通讯作者：
Voudris V
影响因子：
17.1
作者：
Ebert AD;Kodo K;Liang P;Wu H;Huber BC;Riegler J;Churko J;Lee J;de Almeida P;Lan F;Diecke S;Burridge PW;Gold JD;Mochly-Rosen D;Wu JC
通讯作者：
Wu JC
影响因子：
2.9
作者：
Klyosov, AA;Rashkovetsky, LG;Keung, WM
通讯作者：
Keung, WM