Reduction of insulin-like growth factor-i expression in the skeletal muscle of noncachectic patients with chronic heart failure
Reduction of insulin-like growth factor-i expression in the skeletal muscle of noncachectic patients with chronic heart failure
复制标题
DOI：
10.1016/s0735-1097(02)01736-9
复制
发表时间：
2002-04-03
影响因子：
24
通讯作者：
Schuler, G
中科院分区：
文献类型：
--
作者：
Hambrecht, R;Schulze, PC;Schuler, G
我们试图评估胰岛素样生长因子-I（IGF-I）在慢性心力衰竭（CHF）肌肉萎缩中的作用，在严重CHF患者中测定血清浓度和局部肌肉IGF-I表达。骨骼肌废用和炎症激活与细胞因子水平升高有牵连，然而，所涉及的病理机制仍然在很大程度上unknowed.Methods血清IGF-I水平测定竞争性固相免疫法在47例严重CHF（左心室射血分数：小于或等于30%）和15名年龄匹配的健康受试者（HS）。通过实时荧光定量PCR和Western blot分析评估股外侧肌活检组织中胰岛素样生长因子-I和IGF-I受体的表达。（CHF为175 +/- 10 ng/ml，HS为170 12 ng/ml，p = NS），CHF中局部肌肉IGF-I mRNA表达降低52%（6.7 ± 0.4对HS中14.0 ± 0.9任意单位，p < 0.001）。这伴随着IGF-I受体mRNA表达的增加（CHF中为86.8 +/- 5.4对HS中为23.1 +/- 1.8任意单位，p < 0.001）。局部IGF-I表达与肌肉横截面积显著相关（R = 0.75，p = 0.01）。体重指数为25 kg/m2的慢性心力衰竭患者表现出外周生长激素（GH）抵抗的迹象，如血清GH升高和IGF-I水平降低所示。结论CHF患者在血清IGF-I水平正常的情况下，肌肉IGF-I表达显著降低，可能导致肌肉质量的早期损失。这些发现与IGF-I在CHF骨骼肌萎缩中的潜在作用一致。(C)2002年，美国心脏病学会基金会。
OBJECTIVES We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF.BACKGROUND Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown.METHODS Serum levels of IGF-I were measured by competitive solid phase immuno-assay in 47 patients with severe CHF (left ventricular ejection fraction : less than or equal to30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis.RESULTS Although serum IGF-I was not significantly different (175 +/- 10 ng/ml in CHF vs. 170 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 +/- 0.4 vs. 14.0 +/- 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 +/- 5.4 in CHF vs. 23.1 +/- 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of <25 kg/m(2) showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels.CONCLUSIONS In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF. (C) 2002 by the American College of Cardiology Foundation.