Age-associated changes in function, structure and mitochondrial genetic and enzymatic abnormalities in the Fischer 344 x Brown Norway F(1) hybrid rat heart.
Age-associated changes in function, structure and mitochondrial genetic and enzymatic abnormalities in the Fischer 344 x Brown Norway F(1) hybrid rat heart.
复制标题
Fischer 344 x Brown挪威F(1)杂交大鼠心脏的功能、结构以及线粒体遗传和酶异常与年龄相关的变化。
DOI：
10.1006/jmcc.2001.1483
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发表时间：
2002
影响因子：
5
通讯作者：
Aiken,JuddM
中科院分区：
文献类型：
--
作者：
Wanagat,Jonathan;Wolff,MatthewR;Aiken,JuddM
我们假设，大鼠心脏衰老涉及线粒体遗传损伤和线粒体酶功能障碍的个别心肌细胞已被证明以前只在灵长类动物心肌。对5、18和36-38月龄Fischer 344 × Brown Norway F1代杂种大鼠的心肌细胞进行了线粒体遗传和酶异常检查。体内血液动力学测量显示左心室功能的年龄相关变化，而组织学评价显示纤维化面积百分比从5月龄心脏的7%± 5%增加到38月龄大鼠左心室内膜下的38%± 2%。线粒体基因组缺乏8000至9000 bp的一级序列中检测到的组织匀浆从右心室和左心室心肌和这些删除的基因组的丰度随着年龄的增加。心肌组织连续冷冻切片机切片的原位组织化学染色显示个别心肌细胞显示异常，主要是缺乏，细胞色素c氧化酶和琥珀酸脱氢酶的活动。在5 ~ 36 ~ 38月龄，左心室组织化学异常心肌细胞的面积密度从0.05/mm 2增加到0.3/mm 2，主要位于左心室内膜下。Fischer 344×Brown Norway F1杂种大鼠心脏中存在与年龄相关的线粒体遗传和酶异常，提示继发于mtDNA突变的线粒体功能障碍在与年龄相关的心肌细胞丢失和随后的心脏衰老中的作用。
We hypothesized that cardiac aging in the rat involves mitochondrial genetic damage and mitochondrial enzymatic dysfunction of individual cardiomyocytes as has been demonstrated previously only in primate myocardium. Myocardium from Fischer 344 × Brown Norway F1hybrid rats of ages 5, 18 and 36–38 months was examined for mitochondrial genetic and enzymatic abnormalities. In-vivo hemodynamic measurements revealed age-related changes of left ventricular function while histological evaluation demonstrated an increase in percent area fibrosis from 7%±5 in the 5-month-old hearts to 38%±2 in the subendocardium of the left ventricle of 38-month-old rats. Mitochondrial genomes lacking 8000 to 9000 bp of primary sequence were detected in tissue homogenates from right and left ventricular myocardium and the abundance of these deleted genomes increased with age. In-situ histochemical staining of serial cryomicrotome sections of myocardial tissue revealed individual cardiomyocytes displaying abnormal, primarily absent, activities of cytochrome c oxidase and succinate dehydrogenase. The area density of histochemically-abnormal cardiomyocytes increased from 0.05 per mm2to 0.3 per mm2between 5 and 36–38 months of age in the left ventricle, and they were localized primarily to the left ventricular subendocardium. The presence of age-related mitochondrial genetic and enzymatic abnormalities in the Fischer 344×Brown Norway F1hybrid rat heart suggests the role of mitochondrial dysfunction, secondary to mtDNA mutations, in age-related cardiomyocyte loss and subsequent cardiac aging.