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. 1999 Mar;81(3):303–307. doi: 10.1136/hrt.81.3.303

Expression of skeletal muscle sarcoplasmic reticulum calcium-ATPase is reduced in rats with postinfarction heart failure

A Simonini 1, K Chang 1, P Yue 1, C Long 1, B Massie 1
PMCID: PMC1728966  PMID: 10026358

Abstract

OBJECTIVE—To determine whether heart failure in rats is associated with altered expression of the skeletal muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA).
METHODS—SERCA protein and mRNA were examined in the soleus muscles of eight female rats with heart failure induced by coronary artery ligation, six weeks after the procedure (mean (SEM) left ventricular end diastolic pressure 20.4 (2.2) mm Hg) and in six sham operated controls by western and northern analyses, respectively.
RESULTS—SERCA-2a isoform protein was reduced by 16% (112 000 (4000) v 134 000 (2000) arbitrary units, p < 0.001), and SERCA-2a messenger RNA was reduced by 59% (0.24 (0.06) v 0.58 (0.02) arbitrary units, p < 0.001). Although rats with heart failure had smaller muscles (0.54 mg/g v 0.66 mg/g body weight), no difference in locomotor activity was observed.
CONCLUSIONS—These results may explain the previously documented abnormalities in calcium handling in skeletal muscle from animals with the same model of congestive heart failure, and could be responsible for the accelerated muscle fatigue characteristic of patients with heart failure.

 Keywords: skeletal muscle; gene expression; heart failure; calcium-ATPase

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Figure 1  .

Figure 1  

Immunoblot for SERCA-2a protein, showing two sham operated controls (CON) on the left and two heart failure rats (CHF) on the right.

Figure 2  .

Figure 2  

Mean values for the SERCA protein and mRNA in arbitrary units. Both were significantly reduced in the heart failure rats. CON, control; CHF, chronic heart failure.

Figure 3  .

Figure 3  

Northern blot showing reduced β-MHC and SERCA mRNA signals in the chronic heart failure (CHF) animals compared with controls (CON).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson K. P. Management of ectopic atrial tachycardia. J Am Coll Cardiol. 1993 Jul;22(1):93–94. doi: 10.1016/0735-1097(93)90820-q. [DOI] [PubMed] [Google Scholar]
  2. Arai M., Matsui H., Periasamy M. Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure. Circ Res. 1994 Apr;74(4):555–564. doi: 10.1161/01.res.74.4.555. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Buller N. P., Jones D., Poole-Wilson P. A. Direct measurement of skeletal muscle fatigue in patients with chronic heart failure. Br Heart J. 1991 Jan;65(1):20–24. doi: 10.1136/hrt.65.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Drexler H., Riede U., Münzel T., König H., Funke E., Just H. Alterations of skeletal muscle in chronic heart failure. Circulation. 1992 May;85(5):1751–1759. doi: 10.1161/01.cir.85.5.1751. [DOI] [PubMed] [Google Scholar]
  7. Lytton J., Westlin M., Burk S. E., Shull G. E., MacLennan D. H. Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps. J Biol Chem. 1992 Jul 15;267(20):14483–14489. [PubMed] [Google Scholar]
  8. Mancini D. M., Coyle E., Coggan A., Beltz J., Ferraro N., Montain S., Wilson J. R. Contribution of intrinsic skeletal muscle changes to 31P NMR skeletal muscle metabolic abnormalities in patients with chronic heart failure. Circulation. 1989 Nov;80(5):1338–1346. doi: 10.1161/01.cir.80.5.1338. [DOI] [PubMed] [Google Scholar]
  9. Mancini D. M., Walter G., Reichek N., Lenkinski R., McCully K. K., Mullen J. L., Wilson J. R. Contribution of skeletal muscle atrophy to exercise intolerance and altered muscle metabolism in heart failure. Circulation. 1992 Apr;85(4):1364–1373. doi: 10.1161/01.cir.85.4.1364. [DOI] [PubMed] [Google Scholar]
  10. Mason D. T., Zelis R., Longhurst J., Lee G. Cardiocirculatory responses to muscular exercise in congestive heart failure. Prog Cardiovasc Dis. 1977 May-Jun;19(6):475–489. doi: 10.1016/0033-0620(77)90011-1. [DOI] [PubMed] [Google Scholar]
  11. Massie B. M., Simonini A., Sahgal P., Wells L., Dudley G. A. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol. 1996 Jan;27(1):140–145. doi: 10.1016/0735-1097(95)00416-5. [DOI] [PubMed] [Google Scholar]
  12. Massie B., Conway M., Yonge R., Frostick S., Ledingham J., Sleight P., Radda G., Rajagopalan B. Skeletal muscle metabolism in patients with congestive heart failure: relation to clinical severity and blood flow. Circulation. 1987 Nov;76(5):1009–1019. doi: 10.1161/01.cir.76.5.1009. [DOI] [PubMed] [Google Scholar]
  13. Mercadier J. J., Lompré A. M., Duc P., Boheler K. R., Fraysse J. B., Wisnewsky C., Allen P. D., Komajda M., Schwartz K. Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. J Clin Invest. 1990 Jan;85(1):305–309. doi: 10.1172/JCI114429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Minotti J. R., Christoph I., Oka R., Weiner M. W., Wells L., Massie B. M. Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance. J Clin Invest. 1991 Dec;88(6):2077–2082. doi: 10.1172/JCI115537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Minotti J. R., Pillay P., Chang L., Wells L., Massie B. M. Neurophysiological assessment of skeletal muscle fatigue in patients with congestive heart failure. Circulation. 1992 Sep;86(3):903–908. doi: 10.1161/01.cir.86.3.903. [DOI] [PubMed] [Google Scholar]
  16. Minotti J. R., Pillay P., Oka R., Wells L., Christoph I., Massie B. M. Skeletal muscle size: relationship to muscle function in heart failure. J Appl Physiol (1985) 1993 Jul;75(1):373–381. doi: 10.1152/jappl.1993.75.1.373. [DOI] [PubMed] [Google Scholar]
  17. Perreault C. L., Gonzalez-Serratos H., Litwin S. E., Sun X., Franzini-Armstrong C., Morgan J. P. Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure. Circ Res. 1993 Aug;73(2):405–412. doi: 10.1161/01.res.73.2.405. [DOI] [PubMed] [Google Scholar]
  18. Pfeffer M. A., Pfeffer J. M., Fishbein M. C., Fletcher P. J., Spadaro J., Kloner R. A., Braunwald E. Myocardial infarct size and ventricular function in rats. Circ Res. 1979 Apr;44(4):503–512. doi: 10.1161/01.res.44.4.503. [DOI] [PubMed] [Google Scholar]
  19. Rohrer D. K., Hartong R., Dillmann W. H. Influence of thyroid hormone and retinoic acid on slow sarcoplasmic reticulum Ca2+ ATPase and myosin heavy chain alpha gene expression in cardiac myocytes. Delineation of cis-active DNA elements that confer responsiveness to thyroid hormone but not to retinoic acid. J Biol Chem. 1991 May 5;266(13):8638–8646. [PubMed] [Google Scholar]
  20. Simonini A., Long C. S., Dudley G. A., Yue P., McElhinny J., Massie B. M. Heart failure in rats causes changes in skeletal muscle morphology and gene expression that are not explained by reduced activity. Circ Res. 1996 Jul;79(1):128–136. doi: 10.1161/01.res.79.1.128. [DOI] [PubMed] [Google Scholar]
  21. Sullivan M. J., Hawthorne M. H. Exercise intolerance in patients with chronic heart failure. Prog Cardiovasc Dis. 1995 Jul-Aug;38(1):1–22. doi: 10.1016/s0033-0620(05)80011-8. [DOI] [PubMed] [Google Scholar]
  22. Tyler T. D., Tessel R. E. A new device for the simultaneous measurement of locomotor and stereotypic frequency in mice. Psychopharmacology (Berl) 1979 Sep;64(3):285–290. doi: 10.1007/BF00427511. [DOI] [PubMed] [Google Scholar]
  23. Williams J. H., Klug G. A. Calcium exchange hypothesis of skeletal muscle fatigue: a brief review. Muscle Nerve. 1995 Apr;18(4):421–434. doi: 10.1002/mus.880180409. [DOI] [PubMed] [Google Scholar]
  24. Wilson J. R., Fink L., Maris J., Ferraro N., Power-Vanwart J., Eleff S., Chance B. Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance. Circulation. 1985 Jan;71(1):57–62. doi: 10.1161/01.cir.71.1.57. [DOI] [PubMed] [Google Scholar]
  25. de la Bastie D., Levitsky D., Rappaport L., Mercadier J. J., Marotte F., Wisnewsky C., Brovkovich V., Schwartz K., Lompré A. M. Function of the sarcoplasmic reticulum and expression of its Ca2(+)-ATPase gene in pressure overload-induced cardiac hypertrophy in the rat. Circ Res. 1990 Feb;66(2):554–564. doi: 10.1161/01.res.66.2.554. [DOI] [PubMed] [Google Scholar]

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