Vescovo Giorgio, Dalla Libera Luciano
Internal Medicine 1, S. Bortolo Hospital, 36100 Vicenza, Italy.
Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):416-22. doi: 10.1097/01.mco.0000232902.97286.35.
The purpose of this review is to enlighten the mechanisms of muscle wastage in experimental heart failure with attention to skeletal muscle apoptosis and the role of proinflammatory cytokines that trigger apoptosis.
Mechanisms leading to muscle wastage in chronic heart failure include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/transcriptional coactivator PGC1 cascade.
Several mechanisms can lead to muscle wastage in heart failure. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquitin-dependent pathways. Systems controlling ubiquitin/proteasome activation have been described. These are triggered by tumour necrosis factor alpha and growth hormone/insulin-like growth factor 1. However, an important role is played by apoptosis. In humans and experimental models of heart failure programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by tumour necrosis factor alpha and in-vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release.
本综述旨在阐明实验性心力衰竭中肌肉萎缩的机制，重点关注骨骼肌细胞凋亡以及触发凋亡的促炎细胞因子的作用。
导致慢性心力衰竭肌肉萎缩的机制包括细胞因子触发的骨骼肌细胞凋亡，以及泛素/蛋白酶体和非泛素依赖性途径。纤维类型的调节涉及生长激素/胰岛素样生长因子1/钙调神经磷酸酶/转录共激活因子PGC1级联反应。
多种机制可导致心力衰竭中的肌肉萎缩。蛋白质合成与降解之间的失衡起着重要作用。蛋白质降解可通过泛素依赖性和非泛素依赖性途径发生。已描述了控制泛素/蛋白酶体激活的系统。这些由肿瘤坏死因子α以及生长激素/胰岛素样生长因子1触发。然而，细胞凋亡起着重要作用。在人类和心力衰竭实验模型中，已在骨骼肌和间质细胞中发现程序性细胞死亡。细胞凋亡由肿瘤坏死因子α触发，体外实验表明其可由第二信使鞘氨醇诱导。细胞凋亡与心力衰竭综合征的严重程度相关。它涉及半胱天冬酶3和9的激活以及线粒体细胞色素c的释放。
