Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression

Scheubel, R.; Tostlebe, Mike; Simm, Andreas; Rohrbach, Susanne; Prondzinsky, Roland; Gellerich, Frank N.; Silber, RE; Holtz, Juergen

doi:10.1016/s0735-1097(02)02600-1

Cited by 124 publications

(91 citation statements)

References 34 publications

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“…The similarity in CS activity between end-stage HF and control groups (Maurer and Zierz 1994) may be explained by the age differences between groups, because the CS activity increases with age (Marin-Garcia et al 1998). The decrease in mitochondrial content is not the only defect occurring in severe HF as the activity of CI (Scheubel et al 2002) and CIII (Jarreta et al 2000) expressed over the CS activity also significantly decreased.…”

Section: Anatomical Sites In the Heartmentioning

confidence: 98%

“…The first reason is the major differences in history of the disease and degree of decompensation between animals and humans (Scheubel et al 2002). A second could be the special features of human heart mitochondria (vida infra).…”

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

“…End-stage HF was associated with multiple mitochondrial functional injuries, e.g., a decrease of ETC activities per muscle mass, most notably CI (Scheubel et al 2002), CIII (Buchwald et al 1990;Jarreta et al 2000;Marin-Garcia et al 1995), and CIV (Arbustini et al 1998;Quigley et al 2000), and a decrease in OXPHOS capacity in the presence of substrates directing electrons into CI in permeabilized fibers (Saks et al 1991;Sharov et al 2000). Part of the loss of mitochondrial ETC activity or OXPHOS per g of muscle is explainable by a decrease in mitochondrial content occurring also in endstage HF (Kalsi et al 1999;Nascimben et al 1996;Quigley et al 2000).…”

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

“…Interestingly, despite different clinical manifestations, end-stage HF from different etiology (dilated, hypertrophic, or ischemic cardiomyopathies) seems to end up with the same key changes in mitochondrial metabolism (Jarreta et al 2000;Kalsi et al 1999;Scheubel et al 2002;Sharov et al 2000), with the exception of the modification in the ANT isoforms, which is specific to dilated cardiomyopathy (Dörner and Schultheiss 2000).…”

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

“…A few studies have shown that some treatments for severe HF improved mitochondrial function and structure, e.g., longterm implantation of left ventricular assist devices improved OXPHOS capacity (Lee et al 1998), beta-blocker therapy reversed part of the defect in ETC activity (Scheubel et al 2002), and administering a beta-adrenoceptor agonist increases cristae-to-matrix ratio and mitochondrial size (Unverferth et al 1980). An evolving trend in the treatment of cardiac disease is the use of metabolic modulators, including therapeutic targets aimed at improving mitochondrial energy production (reviewed by Murray et al 2007) to prevent or reverse the low energy status of the failing heart.…”

Section: Mitochondrial Function In the Prevention And Treatment Cardimentioning

confidence: 99%

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Mitochondria in the human heart

Lemieux

Hoppel

2009

J Bioenerg Biomembr

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The heart relies mainly on mitochondrial metabolism to provide the energy needed for pumping blood to oxygenate the organs of the body. The study of mitochondrial function in the human heart faces many obstacles and elucidation of the role of mitochondria in cardiac diseases has relied mainly on studies with animal models. Cardiac diseases are the leading cause of mortality worldwide. With the emergence of new therapies to treat and prevent heart disease, some aiming at metabolic modulation, a need for acquiring a better understanding of mitochondrial function in the human heart becomes apparent. Our review is aimed at specific evaluation of the human heart in terms of (1) methods to understand mitochondrial function, with particular emphasis on integrated function, (2) data on the role of mitochondrial dysfunction in cardiovascular disease, and (3) possible applications of this knowledge in the treatment of patients with cardiac disease.

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Section: Anatomical Sites In the Heartmentioning

confidence: 98%

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

Section: Anatomical Sites In the Heartmentioning

confidence: 99%

Section: Mitochondrial Function In the Prevention And Treatment Cardimentioning

confidence: 99%

See 3 more Smart Citations

Mitochondria in the human heart

Lemieux

Hoppel

2009

J Bioenerg Biomembr

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Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

Melenovský

Petrák

Mráček

et al. 2016

European J of Heart Fail

200

158

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Differential effects of right and left heart failure on skeletal muscle in rats

Knapp

Niemann

et al. 2020

J cachexia sarcopenia muscle

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Background Exercise intolerance is a cardinal symptom in right (RV) and left ventricular (LV) failure. The underlying skeletal muscle contributes to increased morbidity in patients. Here, we compared skeletal muscle sarcopenia in a novel two-stage model of RV failure to an established model of LV failure. Methods Pulmonary artery banding (PAB) or aortic banding (AOB) was performed in weanling rats, inducing a transition from compensated cardiac hypertrophy (after 7 weeks) to heart failure (after 22-26 weeks). Cardiac function was characterized by echocardiography. Skeletal muscle catabolic/anabolic balance and energy metabolism were analysed by histological and biochemical methods, real-time PCR, and western blot. Results Two clearly distinguishable stages of left or right heart disease with a comparable severity were reached. However, skeletal muscle impairment was significantly more pronounced in LV failure. While the compensatory stage resulted only in minor changes, soleus and gastrocnemius muscle of AOB rats at the decompensated stage demonstrated reduced weight and fibre diameter, higher proteasome activity and expression of the muscle-specific ubiquitin E3 ligases muscle-specific RING finger 1 and atrogin-1, increased expression of the atrophy marker myostatin, increased autophagy activation, and impaired mitochondrial function and respiratory chain gene expression. Soleus and gastrocnemius muscle of PAB rats did not show significant changes in muscle weight and proteasome or autophagy activation, but mitochondrial function was mildly impaired as well. The diaphragm did not demonstrate differences in any model or disease stage except for myostatin expression, which was altered at the decompensated stage in both models. Plasma interleukin (IL)-6 and angiotensin II were strongly increased at the decompensated stage (AOB > > PAB). Soleus and gastrocnemius muscle itself demonstrated an increase in IL-6 expression independent from blood-derived cytokines only in AOB animals. In vitro experiments in rat skeletal muscle cells suggested a direct impact of IL-6 and angiotensin II on distinctive atrophic changes. Conclusions Manifold skeletal muscle alterations are more pronounced in LV failure compared with RV failure despite a similar ventricular impairment. Most of the catabolic changes were observed in soleus or gastrocnemius muscle rather than in the constantly active diaphragm. Mitochondrial dysfunction and up-regulation of myostatin were identified as the earliest signs of skeletal muscle impairment.

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Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression

Cited by 124 publications

References 34 publications

Mitochondria in the human heart

Mitochondria in the human heart

Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis

Differential effects of right and left heart failure on skeletal muscle in rats

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