Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United States.
Redox Biol. 2014 Jul 19;2:921-8. doi: 10.1016/j.redox.2014.07.002. eCollection 2014.
Peripheral artery disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in the arteries supplying the legs, affects approximately 5% of Americans. We have previously, demonstrated that a myopathy characterized by myofiber oxidative damage and degeneration is central to PAD pathophysiology.
In this study, we hypothesized that increased oxidative damage in the myofibers of the gastrocnemius of PAD patients is myofiber-type selective and correlates with reduced myofiber size.
Needle biopsies were taken from the gastrocnemius of 53 PAD patients (28 with early PAD and 25 with advanced PAD) and 25 controls. Carbonyl groups (marker of oxidative damage), were quantified in myofibers of slide-mounted tissue, by quantitative fluorescence microscopy. Myofiber cross-sectional area was determined from sarcolemma labeled with wheat germ agglutinin. The tissues were also labeled for myosin I and II, permitting quantification of oxidative damage to and relative frequency of the different myofiber Types (Type I, Type II and mixed Type I/II myofibers). We compared PAD patients in early (N=28) vs. advanced (N=25) disease stage for selective, myofiber oxidative damage and altered morphometrics.
The carbonyl content of gastrocnemius myofibers was higher in PAD patients compared to control subjects, for all three myofiber types (p<0.05). In PAD patients carbonyl content was higher (p<0.05) in Type II and I/II fibers compared to Type I fibers. Furthermore, the relative frequency and cross-sectional area of Type II fibers were lower, while the relative frequencies and cross-sectional area of Type I and Type I/II fibers were higher, in PAD compared to control gastrocnemius (p<0.05). Lastly, the type II-selective oxidative damage increased and myofiber size decreased as the disease progressed from the early to advanced stage.
Our data confirm increased myofiber oxidative damage and reduced myofiber size in PAD gastrocnemius and demonstrate that the damage is selective for type II myofibers and is worse in the most advanced stage of PAD.
外周动脉疾病（PAD）是一种全身性动脉粥样硬化的表现，会导致腿部供血动脉阻塞，影响约 5%的美国人。我们之前已经证明，以肌纤维氧化损伤和变性为特征的肌病是 PAD 病理生理学的核心。
在这项研究中，我们假设 PAD 患者的比目鱼肌中的氧化损伤增加是肌纤维类型选择性的，并与肌纤维大小减小相关。
从 53 名 PAD 患者（28 名早期 PAD 患者和 25 名晚期 PAD 患者）和 25 名对照者的比目鱼肌中采集针吸活检标本。通过定量荧光显微镜，在载玻片组织上对肌纤维中的羰基（氧化损伤的标志物）进行量化。用麦胚凝集素标记肌纤维的肌膜，确定肌纤维的横截面积。组织还标记肌球蛋白 I 和 II，允许量化不同肌纤维类型（I 型、II 型和混合 I/II 型肌纤维）的氧化损伤和相对频率。我们比较了早期（N=28）和晚期（N=25）疾病阶段的 PAD 患者，比较了选择性肌纤维氧化损伤和形态计量学的改变。
与对照组相比，所有三种肌纤维类型的 PAD 患者比目鱼肌肌纤维的羰基含量均升高（p<0.05）。在 PAD 患者中，与 I 型纤维相比，II 型纤维和 I/II 纤维的羰基含量更高（p<0.05）。此外，与对照组比目鱼肌相比，PAD 患者的 II 型纤维相对频率和横截面积更低，而 I 型和 I/II 型纤维的相对频率和横截面积更高（p<0.05）。最后，随着疾病从早期到晚期的进展，II 型选择性氧化损伤增加，肌纤维大小减小。
我们的数据证实了 PAD 比目鱼肌中肌纤维氧化损伤增加和肌纤维大小减小，并表明损伤是 II 型肌纤维的选择性损伤，在 PAD 的最晚期阶段更为严重。
