Cardiac aging in mice and humans: the role of mitochondrial oxidative stress.

Cardiac aging in mice and humans: the role of mitochondrial oxidative stress.
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DOI:
10.1016/j.tcm.2009.12.004
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发表时间:
2009-10
影响因子:
9.3
通讯作者:
Rabinovitch, Peter S.
Rabinovitch, Peter S.
中科院分区:
医学2区
文献类型:
--
作者:
Dai, Dao-Fu;Rabinovitch, Peter S.

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年龄是心血管疾病的一个主要风险因素,不仅因为它延长了暴露在其他几种心血管风险中的时间,而且还因为心脏固有的老化,它减少了心脏功能储备,使心脏容易受到压力,并导致老年人心血管死亡率增加。小鼠模型中的内在心脏老化与人类年龄相关的心脏变化密切相关,包括左心室肥厚、纤维化和舒张期功能障碍。小鼠心脏衰老伴随着线粒体蛋白氧化积累、线粒体DNA突变增加、线粒体生物合成增加以及心肌SERCA2蛋白减少。所有这些与年龄相关的变化在过度表达针对线粒体的过氧化氢酶(MCAT)的小鼠中都显著减弱。这些发现证明了线粒体活性氧物种(ROS)在心脏衰老中的关键作用,并支持线粒体抗氧化剂在心脏衰老和与年龄相关的心血管疾病中的潜在应用。
Age is a major risk factor for cardiovascular diseases, not only because it prolongs exposure to several other cardiovascular risks, but also owing to intrinsic cardiac aging, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria (mCAT). These findings demonstrate the critical role of mitochondrial reactive oxygen species (ROS) in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases.
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