Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury.

Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury.
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单胺氧化酶(MAO)在心力衰竭和缺血/再灌注损伤发病机制中的作用。

DOI:
10.1016/j.bbamcr.2010.09.010
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发表时间:
2011-07
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Paolocci N
Paolocci N
中科院分区:
其他
文献类型:
--
作者:
Kaludercic N;Carpi A;Menabò R;Di Lisa F;Paolocci N

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最近的证据表明,单胺氧化酶(MAO)是氧化应激的另一个重要来源。MAO是一类位于线粒体膜外膜上的酶,参与去甲肾上腺素、肾上腺素和多巴胺等关键神经递质的氧化分解,并在此过程中产生过氧化氢。所有这些单胺类物质对心肌功能都有很强的调节作用。因此,当心脏受到慢性神经激素和/或外周血液动力学应激时,循环/组织中丰富的单胺类物质可以使MAO产生的过氧化氢特别突出。这是由于缺血/再灌流损伤造成的急性心脏损害,或者,从更慢性的角度来看,从代偿性肥厚过渡到显性的心室扩张/泵衰竭。在这里,我们将首先简要讨论线粒体的状态及其在急性和慢性心脏疾病中的作用。我们将说明MAO活性影响心脏生物学和功能的可能机制,并讨论它们作为活性氧物种的重要来源的作用。最后,我们将推测为什么MAO抑制可能对治疗缺血性和非缺血性心脏疾病具有治疗价值。
Recent evidence highlights monoamine oxidases (MAO) as another prominent source of oxidative stress. MAO are a class of enzymes located in the outer mitochondrial membrane, deputed to the oxidative breakdown of key neurotransmitters such as norepinephrine, epinephrine and dopamine, and in the process generate H2O2. All these monoamines are endowed with potent modulatory effects on myocardial function. Thus, when the heart is subjected to chronic neuro-hormonal and/or peripheral hemodynamic stress, the abundance of circulating/tissue monoamines can make MAO-derived H2O2 production particularly prominent. This is the case of acute cardiac damage due to ischemia/reperfusion injury or, on a more chronic stand, of the transition from compensated hypertrophy to overt ventricular dilation/pump failure. Here, we will first briefly discuss mitochondrial status and contribution to acute and chronic cardiac disorders. We will illustrate possible mechanisms by which MAO activity affects cardiac biology and function, along with a discussion as to their role as a prominent source of reactive oxygen species. Finally, we will speculate on why MAO inhibition might have therapeutic value for treating cardiac affections of ischemic and non-ischemic origin.
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