Clinical InvestigationAbnormalities of Calcium Handling Proteins in Skeletal Muscle Mirror Those of the Heart in Humans With Heart Failure: A Shared Mechanism?
Section snippets
Study Population
Advanced HF patients, New York Heart Association Class II-III who met the following criteria were recruited from the Ahmanson-UCLA Cardiomyopathy Center: 1) age 21 to 65 years, 2) left ventricular ejection fraction ≤35%, 3) HF duration ≥ 6 months, 4) no active ischemia or ischemic event within 3 months, 5) not involved in a formal exercise training program, 6) on stable HF medications for ≥ 3 months, and 7) not taking warfarin. Age- and sex-matched healthy, nonsmoking controls, without chronic
Study Population Characteristics
Ten advanced HF patients and 9 healthy controls participated in these studies. Study population characteristics are displayed in Table 2. Patients and controls did not differ in age, sex, or body mass index. Of note, patients had chronic HF (mean duration 9.5 ± 1.9 years) and had severe exercise limitation as estimated by peak oxygen consumption of 11.6 ± 1.0 mL·kg·min.
Morphometric Analysis
Individual mean type 1 fiber percentage is shown in Figure 1a. Mean type 1 fiber type percentage in our HF patients was 30.6 ±
Discussion
The major, novel findings in this study of chronic, advanced HF patients on optimal medical therapy with severely limited exercise tolerance are: 1) SERCA2a and DHPR protein content in skeletal muscle are significantly decreased in HF patients compared with healthy controls, 2) p-PLN content and the p-PLN/PLN ratio in skeletal muscle are markedly decreased in HF patients compared with healthy controls, and 3) the lack of increase, and in fact significant decrease, in HSP and ROS scavenger
Acknowledgments
The authors wish to thank Dr. James N. Weiss for his insights and thoughtful comments on this work.
Disclosures
None.
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Supported by NIH-RO1 HL084525 (H.R.M.), the University of California, Los Angeles, General Clinical Research Center NIH-MO1-RR00865, and the Natural Sciences and Engineering Research Council of Canada (NSERC) 311922 (A.R.T.). C. Vigna was supported by a PGS-D award from NSERC.
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