Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.
Monoamine oxidase is a major determinant of redox balance in human atrial myocardium and is associated with postoperative atrial fibrillation.
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DOI：
10.1161/jaha.113.000713
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发表时间：
2014-02-26
影响因子：
5.4
通讯作者：
Kypson AP
中科院分区：
文献类型：
--
作者：
Anderson EJ;Efird JT;Davies SW;O'Neal WT;Darden TM;Thayne KA;Katunga LA;Kindell LC;Ferguson TB;Anderson CA;Chitwood WR;Koutlas TC;Williams JM;Rodriguez E;Kypson AP
术后房颤（POAF）的发生是心脏手术的常见并发症，尽管手术技术和患者护理质量有了很大的改进，但费用昂贵。POAF的病因以及临床医生识别和治疗高危患者的能力仍然难以捉摸。从244例心脏手术患者的右心耳（RAA）中分离出心肌组织。在该组织中评估了多种来源的活性氧（ROS）生成，沿着总谷胱甘肽（GSHt）及其相关酶谷胱甘肽过氧化物酶（GPx）和谷胱甘肽还原酶（GR）。观察到单胺氧化酶（MAO）和NADPH氧化酶产生活性氧的速率比完整的偶联线粒体高10倍。POAF风险与MAO活性显著相关（四分位数1 [Q1]：校正的相对风险[ARR]=1.0; Q2：ARR=1.8，95%置信区间[CI]=0.84 - 4.0; Q3：ARR=2.1，95% CI=0.99 - 4.3; Q4：ARR=3.8，95% CI=1.9 - 7.5;校正的P趋势=0.009）。相反，心肌GSHt与POAF呈负相关（四分位数1 [Q1]：校正的相对危险度[ARR]=1.0; Q2：ARR=0.93，95%置信区间[CI]=0.60 - 1.4; Q3：ARR=0.62，95% CI=0.36 - 1.1; Q4：ARR=0.56，95% CI=0.34 - 0.93;校正的P趋势=0.014）。GPx也与POAF显著相关;然而，在增加酶水平时未观察到风险的线性趋势。GR与POAF风险无关。我们的研究结果表明，单胺氧化酶是人类心房肌氧化还原平衡的一个重要决定因素，这种酶，除了谷胱甘肽和GPx，与POAF的风险增加。需要进一步的研究来验证MAO作为POAF的预测生物标志物，并探索这种酶在卵巢发生中的潜在作用。
Onset of postoperative atrial fibrillation (POAF) is a common and costly complication of heart surgery despite major improvements in surgical technique and quality of patient care. The etiology of POAF, and the ability of clinicians to identify and therapeutically target high‐risk patients, remains elusive. Myocardial tissue dissected from right atrial appendage (RAA) was obtained from 244 patients undergoing cardiac surgery. Reactive oxygen species (ROS) generation from multiple sources was assessed in this tissue, along with total glutathione (GSHt) and its related enzymes GSH‐peroxidase (GPx) and GSH‐reductase (GR). Monoamine oxidase (MAO) and NADPH oxidase were observed to generate ROS at rates 10‐fold greater than intact, coupled mitochondria. POAF risk was significantly associated with MAO activity (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=1.8, 95% confidence interval [CI]=0.84 to 4.0; Q3: ARR=2.1, 95% CI=0.99 to 4.3; Q4: ARR=3.8, 95% CI=1.9 to 7.5; adjusted Ptrend=0.009). In contrast, myocardial GSHt was inversely associated with POAF (Quartile 1 [Q1]: adjusted relative risk [ARR]=1.0; Q2: ARR=0.93, 95% confidence interval [CI]=0.60 to 1.4; Q3: ARR=0.62, 95% CI=0.36 to 1.1; Q4: ARR=0.56, 95% CI=0.34 to 0.93; adjusted Ptrend=0.014). GPx also was significantly associated with POAF; however, a linear trend for risk was not observed across increasing levels of the enzyme. GR was not associated with POAF risk. Our results show that MAO is an important determinant of redox balance in human atrial myocardium, and that this enzyme, in addition to GSHt and GPx, is associated with an increased risk for POAF. Further investigation is needed to validate MAO as a predictive biomarker for POAF, and to explore this enzyme's potential role in arrhythmogenesis.