Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease.
Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease.
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外周动脉疾病患者胃癌中的氧化损伤和肌纤维变性。
DOI：
10.1186/1479-5876-11-230
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发表时间：
2013-09-25
影响因子：
7.4
通讯作者：
Pipinos II
中科院分区：
文献类型：
--
作者：
Weiss DJ;Casale GP;Koutakis P;Nella AA;Swanson SA;Zhu Z;Miserlis D;Johanning JM;Pipinos II
外周动脉疾病(PAD)是系统性动脉粥样硬化的一种表现，会导致腿部供应动脉阻塞，在欧洲和北美估计有2700万人受到影响。PAD患者腿部肌肉中功能障碍的线粒体产生的活性氧增加被认为是疾病发生和发展的关键机制。先前的研究表明，与对照组相比，PAD腓肠肌活检标本的匀浆中的氧化损伤增加，但没有解决肌纤维特异性损伤。在这项研究中，我们研究了肌肉纤维的氧化损伤作为PAD肌病的可能原因。为了实现这一点，我们开发并验证了荧光显微镜方法，用于定量分析来自人腓肠肌活检标本的肌纤维中的羰基和4-羟基-2-壬烯醛(HNE)加合物。评估PAD和对照标本在1)这两种形式的氧化损伤的肌纤维含量和2)肌纤维横截面积方面的差异。此外，对PAD肌纤维的氧化损伤与临床疾病分期、患肢缺血程度和肌纤维横截面积的相关性进行了测试。与对照组(N )相比，PAD患者(N = 34)肌纤维中的羰基和HNE加合物分别增加了30%(p = <； 0.0001)和40%(p = <； = 0.0001)。与对照组相比，PAD肌纤维的平均横截面积减少了29.3%(p <； 0.0003)。这两种形式的氧化损伤都随着疾病的临床分期、缺血小腿的血流受限和肌纤维横截面积的减少而增加。这些数据表明，肌肉纤维的氧化损伤可能是PAD肌病的一个原因。
Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in arteries supplying the legs, affects an estimated 27 million people in Europe and North America. Increased production of reactive oxygen species by dysfunctional mitochondria in leg muscles of PAD patients is viewed as a key mechanism of initiation and progression of the disease. Previous studies demonstrated increased oxidative damage in homogenates of biopsy specimens from PAD gastrocnemius compared to controls, but did not address myofiber-specific damage. In this study, we investigated oxidative damage to myofibers as a possible cause of the myopathy of PAD. To achieve this, we developed and validated fluorescence microscopy procedures for quantitative analysis of carbonyl groups and 4-hydroxy-2-nonenal (HNE) adducts in myofibers of biopsy specimens from human gastrocnemius. PAD and control specimens were evaluated for differences in 1) myofiber content of these two forms of oxidative damage and 2) myofiber cross-sectional area. Furthermore, oxidative damage to PAD myofibers was tested for associations with clinical stage of disease, degree of ischemia in the affected leg, and myofiber cross-sectional area. Carbonyl groups and HNE adducts were increased 30% (p < 0.0001) and 40% (p < 0.0001), respectively, in the myofibers of PAD (N = 34) compared to control (N = 21) patients. Mean cross-sectional area of PAD myofibers was reduced 29.3% compared to controls (p < 0.0003). Both forms of oxidative damage increased with clinical stage of disease, blood flow limitation in the ischemic leg, and reduced myofiber cross-sectional area. The data establish oxidative damage to myofibers as a possible cause of PAD myopathy.
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影响因子：
4.1
作者：
LoPachin, Richard M.;Gavin, Terrence;Petersen, Dennis R.;Barber, David S.
通讯作者：
Barber, David S.
DOI：
10.1111/j.1582-4934.2006.tb00407.x
发表时间：
2006-04
影响因子：
5.3
作者：
Dalle-Donne I;Aldini G;Carini M;Colombo R;Rossi R;Milzani A
通讯作者：
Milzani A
影响因子：
4.3
作者：
Bauer, TA;Brass, EP;Hiatt, WR
通讯作者：
Hiatt, WR
影响因子：
4.8
作者：
Hashimoto, M;Sibata, T;Uchida, K
通讯作者：
Uchida, K
影响因子：
4.3
作者：
McDermott, MM;Criqui, MH;Schneider, JR
通讯作者：
Schneider, JR