Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity.
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 +/- 3 yr) and 11 controls (70 +/- 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 = -0.748, P < 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 = -0.442, P = 0.05) and the ratio of MHC to mixed muscle protein synthesis (r = -0.493, P < 0.03). Heart failure patients showed reduced relative amounts of MHC I (P < 0.05) and a trend toward increased MHC IIx (P = 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.
Toth
Michael J
MJ
Health Science Research Facility 126 B, 149 Beaumont Ave., University of Vermont, Burlington, VT 05405, USA. michael.toth@uvm.edu
Matthews
Dwight E
DE
Ades
Philp A
PA
Tischler
Marc D
MD
Van Buren
Peter
P
Previs
Michael
M
LeWinter
Martin M
MM
D000199:Actins / Q000276:immunology / Q000378:metabolism; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D006333:Heart Failure / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000276:immunology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D020033:Protein Isoforms; D019947:Receptors, Interleukin-6 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D015850:Interleukin-6; D020033:Protein Isoforms; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D018995:Myosin Heavy Chains