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Ventricular assist device implantation improves skeletal muscle function, oxidative capacity, and growth hormone/insulin-like growth factor-1 axis signaling in patients with advanced heart failure.
Journal of Cachexia, Sarcopenia and Muscle ( IF 8.9 ) Pub Date : 2014-08-07 , DOI: 10.1007/s13539-014-0155-9 Tuba Khawaja 1 , Aalap Chokshi , Ruiping Ji , Tomoko S Kato , Katherine Xu , Cynthia Zizola , Christina Wu , Daniel E Forman , Takeyoshi Ota , Peter Kennel , Hiroo Takayama , Yoshifumi Naka , Isaac George , Donna Mancini , Christian P Schulze
Journal of Cachexia, Sarcopenia and Muscle ( IF 8.9 ) Pub Date : 2014-08-07 , DOI: 10.1007/s13539-014-0155-9 Tuba Khawaja 1 , Aalap Chokshi , Ruiping Ji , Tomoko S Kato , Katherine Xu , Cynthia Zizola , Christina Wu , Daniel E Forman , Takeyoshi Ota , Peter Kennel , Hiroo Takayama , Yoshifumi Naka , Isaac George , Donna Mancini , Christian P Schulze
Affiliation
BACKGROUND
Skeletal muscle dysfunction in patients with heart failure (HF) has been linked to impaired growth hormone (GH)/insulin-like growth factor (IGF)-1 signaling. We hypothesized that ventricular assist device (VAD) implantation reverses GH/IGF-1 axis dysfunction and improves muscle metabolism in HF.
METHODS
Blood and rectus abdominis muscle samples were collected during VAD implantation and explantation from patients with HF and controls. Clinical data were obtained from medical records, biomarkers measured by enzyme-linked immunosorbent assay (ELISA), and gene expression analyzed by reverse transcription and real-time polymerase chain reaction (RT-PCR). Grip strength was assessed by dynamometry. Oxidative capacity was measured using oleate oxidation rates. Muscle fiber type and size were assessed by histology.
RESULTS
Elevated GH (0.27 ± 0.27 versus 3.6 ± 7.7 ng/ml in HF; p = 0.0002) and lower IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 were found in HF (IGF-1, 144 ± 41 versus 74 ± 45 ng/ml in HF, p < 0.05; and IGFBP-3, 3,880 ± 934 versus 1,935 ± 862 ng/ml in HF, p = 0.05). The GH/IGF-1 ratio, a marker of GH resistance, was elevated in HF (0.002 ± 0.002 versus 0.048 ± 0.1 pre-VAD; p < 0.0039). After VAD support, skeletal muscle expression of IGF-1 and IGFBP-3 increased (10-fold and 5-fold, respectively; p < 0.05) accompanied by enhanced oxidative gene expression (CD36, CPT1, and PGC1α) and increased oxidation rates (+1.37-fold; p < 0.05). Further, VAD implantation increased the oxidative muscle fiber proportion (38 versus 54 %, p = 0.031), fiber cross-sectional area (CSA) (1,005 ± 668 versus 1,240 ± 670 μm(2), p < 0.001), and Akt phosphorylation state in skeletal muscle. Finally, hand grip strength increased 26.5 ± 27.5 % at 180 days on-VAD (p < 0.05 versus baseline).
CONCLUSION
Our data demonstrate that VAD implantation corrects GH/IGF-1 signaling, improves muscle structure and function, and enhances oxidative muscle metabolism in patients with advanced HF.
中文翻译:
心室辅助装置植入可改善晚期心力衰竭患者的骨骼肌功能、氧化能力和生长激素/胰岛素样生长因子-1 轴信号。
背景 心力衰竭 (HF) 患者的骨骼肌功能障碍与受损的生长激素 (GH)/胰岛素样生长因子 (IGF)-1 信号传导有关。我们假设心室辅助装置 (VAD) 植入可逆转 GH/IGF-1 轴功能障碍并改善 HF 中的肌肉代谢。方法 在 VAD 植入和摘除期间从 HF 患者和对照组收集血液和腹直肌样本。临床数据来自医疗记录、酶联免疫吸附试验 (ELISA) 测量的生物标志物以及逆转录和实时聚合酶链反应 (RT-PCR) 分析的基因表达。握力通过测力法评估。使用油酸氧化速率测量氧化能力。通过组织学评估肌肉纤维类型和大小。结果 GH升高(0. 27 ± 0.27 与 3.6 ± 7.7 ng/ml HF;p = 0.0002) 并且在 HF 中发现较低的 IGF-1 和胰岛素样生长因子结合蛋白 (IGFBP)-3(IGF-1,144 ± 41 对比 74 ± 45 ng/ml HF,p < 0.05;和 IGFBP -3, 3,880 ± 934 与 1,935 ± 862 ng/ml HF,p = 0.05)。GH/IGF-1 比率(GH 抵抗的标志物)在 HF 中升高(0.002 ± 0.002 与 0.048 ± 0.1 前 VAD;p < 0.0039)。在 VAD 支持后,IGF-1 和 IGFBP-3 的骨骼肌表达增加(分别为 10 倍和 5 倍;p < 0.05),伴随着氧化基因表达(CD36、CPT1 和 PGC1α)的增加和氧化速率的增加( +1.37 倍;p < 0.05)。此外,VAD 植入增加了氧化肌纤维比例(38 % 对 54 %,p = 0.031)、纤维横截面积 (CSA)(1,005 ± 668 对 1,240 ± 670 μm(2),p < 0.001),和骨骼肌中的 Akt 磷酸化状态。最后,在 VAD 治疗 180 天时,手握力增加了 26.5 ± 27.5%(与基线相比,p < 0.05)。结论 我们的数据表明,VAD 植入可纠正 GH/IGF-1 信号传导,改善肌肉结构和功能,并增强晚期 HF 患者的肌肉氧化代谢。
更新日期:2019-11-01
中文翻译:
心室辅助装置植入可改善晚期心力衰竭患者的骨骼肌功能、氧化能力和生长激素/胰岛素样生长因子-1 轴信号。
背景 心力衰竭 (HF) 患者的骨骼肌功能障碍与受损的生长激素 (GH)/胰岛素样生长因子 (IGF)-1 信号传导有关。我们假设心室辅助装置 (VAD) 植入可逆转 GH/IGF-1 轴功能障碍并改善 HF 中的肌肉代谢。方法 在 VAD 植入和摘除期间从 HF 患者和对照组收集血液和腹直肌样本。临床数据来自医疗记录、酶联免疫吸附试验 (ELISA) 测量的生物标志物以及逆转录和实时聚合酶链反应 (RT-PCR) 分析的基因表达。握力通过测力法评估。使用油酸氧化速率测量氧化能力。通过组织学评估肌肉纤维类型和大小。结果 GH升高(0. 27 ± 0.27 与 3.6 ± 7.7 ng/ml HF;p = 0.0002) 并且在 HF 中发现较低的 IGF-1 和胰岛素样生长因子结合蛋白 (IGFBP)-3(IGF-1,144 ± 41 对比 74 ± 45 ng/ml HF,p < 0.05;和 IGFBP -3, 3,880 ± 934 与 1,935 ± 862 ng/ml HF,p = 0.05)。GH/IGF-1 比率(GH 抵抗的标志物)在 HF 中升高(0.002 ± 0.002 与 0.048 ± 0.1 前 VAD;p < 0.0039)。在 VAD 支持后,IGF-1 和 IGFBP-3 的骨骼肌表达增加(分别为 10 倍和 5 倍;p < 0.05),伴随着氧化基因表达(CD36、CPT1 和 PGC1α)的增加和氧化速率的增加( +1.37 倍;p < 0.05)。此外,VAD 植入增加了氧化肌纤维比例(38 % 对 54 %,p = 0.031)、纤维横截面积 (CSA)(1,005 ± 668 对 1,240 ± 670 μm(2),p < 0.001),和骨骼肌中的 Akt 磷酸化状态。最后,在 VAD 治疗 180 天时,手握力增加了 26.5 ± 27.5%(与基线相比,p < 0.05)。结论 我们的数据表明,VAD 植入可纠正 GH/IGF-1 信号传导,改善肌肉结构和功能,并增强晚期 HF 患者的肌肉氧化代谢。