|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2002; 40:2174-2181 © 2002 by the American College of Cardiology Foundation |
,*
* Cardio-Thoracic Surgery, Halle/Saale, Germany
Cardiology, Halle/Saale, Germany
Neurology , Halle/Saale, Germany
Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany
Manuscript received May 7, 2002; revised manuscript received July 24, 2002, accepted August 11, 2002.
* Reprint requests and correspondence: Dr. Robert J. Scheubel, Klinik für Herz- und Thoraxchirurgie, Martin-Luther-Universitaet Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097 Halle (Saale), Germany.
robert.scheubel{at}medizin.uni-halle.de
OBJECTIVES: Activity of mitochondrial respiratory chain complexes with and without mitochondrially encoded subunits was assessed in failing human myocardium together with parameters of mitochondrial gene expression.
BACKGROUND: Mutations and deletions in mitochondrial genome (mtDNA) sporadically accumulate in the aging myocardium. In experimental heart failure, they are discussed to be a generalized problem resulting in disturbances of mitochondrial gene expression and mitochondrial function.
METHODS: In left ventricular specimens from 43 explanted failing hearts and 10 donor hearts, enzyme activities of respiratory chain complexes, messenger ribonucleic acid (mRNA) expression of mitochondrially and nuclear encoded mitochondrial components (reverse transcriptase-polymerase chain reaction, Northern blot), undeleted wildtype mtDNA (Southern blot), and nuclear encoded mitochondrial transcription factor A (mtTFA) (Western blot) were quantified.
RESULTS: Citrate synthase normalized activity of mitochondrial respiratory chain complex I, which contains seven mitochondrially encoded subunits, was decreased by 28% in terminally failing myocardium, whereas the activity of the exclusively nuclear encoded complex II was unchanged. However, the amount of intact mtDNA, the mRNA of all mitochondrially encoded subunits of the entire respiratory chain, the amount of mtTFA, and the enzymatic activity of complex III and complex IV, which also contain mitochondrially encoded subunits, were normal compared with donor hearts, excluding generalized disturbance of mitochondrial gene expression. Retrospective analysis of drug therapy before transplantation identified beta-blockers as one putative protection against this disturbance.
CONCLUSIONS: In terminally failing human myocardium of patients receiving drug therapy, complex I depression is not caused by mtDNA damage and disturbed mitochondrial gene expression. The absence of mtDNA damage should facilitate recovery of the overloaded myocardium, if effective unloading could be achieved.
| ||||||||||||||||||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  M. G. Rosca, E. J. Vazquez, J. Kerner, W. Parland, M. P. Chandler, W. Stanley, H. N. Sabbah, and C. L. Hoppel Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation Cardiovasc Res, October 1, 2008; 80(1): 30 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Wall, J. Wei, M. Ly, P. Belmont, J. J. Martindale, D. Tran, J. Sun, W. J. Chen, W. Yu, P. Oeller, et al. Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6 Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2462 - H2472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Di Lisa and P. Bernardi Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition Cardiovasc Res, May 1, 2005; 66(2): 222 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Moe, J. Marin-Garcia, A. Konig, M. Goldenthal, X. Lu, and Q. Feng In vivo TNF-{alpha} inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1813 - H1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. van Bilsen, P. J.H Smeets, A. J Gilde, and G. J van der Vusse Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res, February 1, 2004; 61(2): 218 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fosslien Mitochondrial Medicine - Cardiomyopathy Caused by Defective Oxidative Phosphorylation Ann. Clin. Lab. Sci., October 1, 2003; 33(4): 371 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Scheubel Reply J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2299 - 2299. [Full Text] [PDF]
|
|
|
|
|
|
J. Marin-Garcia Mitochondrial dysfunction in heart failure J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2299 - 2299. [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
