LeWinter. Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity. Am J Physiol Endocrinol Metab 288: E685-E692, 2005. First published November 23, 2004; doi:10.1152/ajpendo.00444.2004.-Chronic heart failure is characterized by changes in skeletal muscle that contribute to physical disability. Most studies to date have investigated defects in skeletal muscle oxidative capacity. In contrast, less is known about how heart failure affects myofibrillar protein metabolism. Thus we examined the effect of heart failure on skeletal muscle myofibrillar protein metabolism, with a specific emphasis on changes in myosin heavy chain (MHC) protein content, synthesis, and isoform distribution in 10 patients with heart failure (63 Ϯ 3 yr) and 11 controls (70 Ϯ 3 yr). In addition, we examined the relationship of MHC protein metabolism to inflammatory markers and physical function. Although MHC and actin protein content did not differ between groups, MHC protein content decreased with increasing disease severity in heart failure patients (r ϭ Ϫ0.748, P Ͻ 0.02), whereas actin protein content was not related to disease severity. No difference in MHC protein synthesis was found between groups, and MHC protein synthesis rates were not related to disease severity. There were, however, relationships between C-reactive protein and both MHC protein synthesis (r ϭ Ϫ0.442, P ϭ 0.05) and the ratio of MHC to mixed muscle protein synthesis (r ϭ Ϫ0.493, P Ͻ 0.03). Heart failure patients showed reduced relative amounts of MHC I (P Ͻ 0.05) and a trend toward increased MHC IIx (P ϭ 0.06). In regression analyses, decreased MHC protein content was related to decreased exercise capacity and muscle strength in heart failure patients. Our results demonstrate that heart failure affects both the quantity and isoform distribution of skeletal muscle MHC protein.The fact that MHC protein content was related to both exercise capacity and muscle strength further suggests that quantitative alterations in MHC protein may have functional significance. sarcopenia; cardiac cachexia; myosin heavy chain isoform; cytokine; actin RESEARCH OVER THE PAST TWO DECADES has identified an important role for skeletal muscle in reduced functional capacity in heart failure patients. Several abnormalities intrinsic to skeletal muscle, including muscle atrophy (7, 30) and diminished oxidative capacity (35), have been cited as factors contributing to physical disability. The mechanisms underlying these defects and their contribution to exercise intolerance and reduced muscle strength, however, remain unclear. The majority of studies that have examined the effect of heart failure on skeletal muscle have focused on oxidative capacity and/or mitochondrial function. In contrast, less is known about the impact of heart failure on myofibrillar proteins and their relationship to reduced functional capacity.Protein is the primary structural and functional macromolecule in skeletal muscle. From both quantitative and funct...
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