Schulze P Christian, Späte Ulrike
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.
Int J Biochem Cell Biol. 2005 Oct;37(10):2023-35. doi: 10.1016/j.biocel.2005.04.017.
Chronic heart failure is a clinical syndrome of cardiac origin, which affects various organ systems. It is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. As in several other chronic diseases, skeletal muscle dysfunction and structural muscle abnormalities result in progressive muscle wasting and cachexia. These changes are accompanied by increased expression of proinflammatory cytokines, increased rate of apoptosis and activation of the proteolytic ubiquitin-proteasome pathway. Further, reduced expression of the local anabolic insulin-like growth factor-1 has been demonstrated in skeletal muscle of animals and patients with chronic heart failure. This suppression occurs in the presence of normal serum levels of insulin-like growth factor-1. In addition to catabolic effects of proinflammatory cytokines, these recent findings are consistent with reduced anabolism involving altered local insulin-like growth factor-1 levels in progressive muscle atrophy in chronic heart failure. This article describes local effects of insulin-like growth factor-1 on skeletal muscle function and morphology, its role in stem cell recruitment and muscle regeneration as well as its regulation in circumstances of muscle inflammation and wasting.
慢性心力衰竭是一种源于心脏的临床综合征，会影响多个器官系统。它与代谢异常相关，在疾病晚期会导致分解代谢综合征。与其他几种慢性疾病一样，骨骼肌功能障碍和肌肉结构异常会导致进行性肌肉萎缩和恶病质。这些变化伴随着促炎细胞因子表达增加、细胞凋亡率升高以及蛋白水解泛素-蛋白酶体途径的激活。此外，在动物和慢性心力衰竭患者的骨骼肌中，已证实局部合成代谢的胰岛素样生长因子-1表达降低。这种抑制在胰岛素样生长因子-1血清水平正常的情况下也会发生。除了促炎细胞因子的分解代谢作用外，这些最新发现与慢性心力衰竭进行性肌肉萎缩中涉及局部胰岛素样生长因子-1水平改变的合成代谢减少相一致。本文描述了胰岛素样生长因子-1对骨骼肌功能和形态的局部影响、其在干细胞募集和肌肉再生中的作用以及在肌肉炎症和萎缩情况下的调节。
