SKELETAL MUSCLE PROTEIN METABOLISM IN HEART FAILURE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究提出的总体假设是，心力衰竭患者的特点是骨骼肌蛋白质代谢的改变，促进了骨骼肌蛋白质的数量和质量的变化。拟议的研究将在恶病质和非恶病质心力衰竭患者和健康对照身上进行。恶病质患者的特征是体重减轻，骨骼肌重减少；而非恶病质患者的特征是体重稳定，骨骼肌重正常。在这个实验模型中，恶病质心力衰竭患者特有的骨骼肌蛋白质代谢的改变代表了导致骨骼肌蛋白质数量和质量变化的可能机制。非恶病质患者作为疾病对照组，健康志愿者作为非疾病对照组。需要检验的主要假设是，吸收后状态的肌肉蛋白质分解代谢增加，餐后状态的蛋白质合成代谢减少，使心力衰竭患者容易失去骨骼肌蛋白质。骨骼肌蛋白质平衡将在吸收后(即24小时禁食)和模拟餐后条件(即正常血糖高胰岛素血症伴随高氨基酸血症)条件下使用稳定同位素示踪剂和前臂平衡技术相结合来测量。另一个有待检验的假设是，与健康对照组相比，心力衰竭患者骨骼肌肌球蛋白重链合成减少。骨骼肌肌球蛋白重链合成将通过测量稳定的同位素标记的亮氨酸掺入骨骼肌蛋白质来评估。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall hypothesis put forth in this study is that heart failure patients are characterized by alterations in skeletal muscle protein metabolism that promote changes in the quantity and quality of skeletal muscle protein. The proposed studies will be performed on cachectic and non-cachectic heart failure patients and healthy controls. Cachectic patients will be characterized by weight loss and reduced skeletal muscle mass; whereas, non-cachectic patients will be characterized by weight stability and normal skeletal muscle mass. In this experimental model, alterations in skeletal muscle protein metabolism specific to cachectic heart failure patients represent possible mechanisms contributing to changes in skeletal muscle protein quantity and quality. Non-cachectic patients serve as a diseased control group and healthy volunteers as a non-diseased control group. The primary hypothesis to be tested is that increased muscle protein catabolism in the postabsorptive state and reduced protein anabolism in the postprandial state predispose heart failure patients to lose skeletal muscle protein. Skeletal muscle protein balance will be measured during postabsorptive (i.e. 24 hour fast) and simulated-postprandial (i.e., euglycemic hyperinsulinemia with concomitant hyperaminoacidemia) conditions using a combination of stable isotope tracer and forearm balance techniques. A secondary hypothesis to be tested is that skeletal muscle myosin heavy chain synthesis is reduced in heart failure patients compared to healthy controls. Skeletal muscle myosin heavy chain synthesis will be assessed by measuring the incorporation of stable isotopically-labeled leucine into skeletal muscle proteins.