Abnormal Mitochondrial Respiration in Failed Human Myocardium

Sharov, Victor G.; Todor, Anastassia; Silverman, Norman A.; Goldstein, Sidney; Sabbah, Hani N.

doi:10.1006/jmcc.2000.1266

Cited by 179 publications

(148 citation statements)

References 34 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…In end-stage heart failure (HF) patients undergoing transplantation, the rate of respiration in fibers per mg protein (Sharov et al 2000) or in isolated mitochondria per mg mitochondrial protein (Lee et al 1998) was similar in both ventricles. In fibers from atrial appendages, the respiration rate with all substrates is lower compared to ventricles, showing the decrease in mitochondrial content, but when OXPHOS was corrected for the amount of mitochondria (using the maximum uncoupled respiration) the respiration was similar in the three chambers .…”

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%

“…The proposed uncoupling in heart disease is supported by increased cardiac levels of uncoupling protein 3 in patients undergoing coronary artery bypass surgery (Murray et al 2004). While the decrease in respiratory control in end-stage HF has been used in support of uncoupling (Murray et al 2007), the decrease in respiratory control is explained by the decrease in State 3 respiration rather than by an increase in leakage (Sharov et al 2000); this is not uncoupling. Other evidence also shows that coupling is preserved in HF mitochondria (Chidsey et al 1966) even at a late stage of the disease .…”

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%

See 3 more Smart Citations

Mitochondria in the human heart

Lemieux

Hoppel

2009

J Bioenerg Biomembr

View full text Add to dashboard Cite

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.

show abstract

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: Anatomical Sites In the Heartmentioning

confidence: 99%

See 2 more Smart Citations

Mitochondria in the human heart

Lemieux

Hoppel

2009

J Bioenerg Biomembr

View full text Add to dashboard Cite

show abstract

“…It is a chronic syndrome in which the heart is not able to satisfy the metabolic and functional needs of the body.Regarding energy metabolism and mitochondrial biogenesis studies, there seems to be a consensus. Mitochondrial function is dramatically altered either in failing hearts of the dog (Marin et al, 2001;Sharov et al, 1998) rodent (De et al, 1999Garnier et al, 2003;Javadov et al, 2005;Jullig et al, 2008) and human (Mettauer et al, 2006;Sharov et al, 2000).…”

Section: Mitochondrial Degeneration In Heart Failurementioning

confidence: 99%

Mitochondrial Biogenesis in Heart: Way of Nurturing and Failure

Sharma¹,

Swarup²

2016

Int.J.Curr.Microbiol.App.Sci

View full text Add to dashboard Cite

Effects of elamipretide on skeletal muscle in dogs with experimentally induced heart failure

et al. 2019

Self Cite

View full text Add to dashboard Cite

Aims Elamipretide (ELAM), an aromatic–cationic tetrapeptide, interacts with cardiolipin and normalizes dysfunctional mitochondria of cardiomyocytes. This study examined the effects of ELAM on skeletal muscle mitochondria function in dogs with chronic heart failure (HF). Methods and results Studies were performed in skeletal muscle biopsy specimens obtained from normal dogs ( n = 7) and dogs with chronic intracoronary microembolization‐induced HF ( n = 14) treated with subcutaneous ELAM 0.5 mg/kg (HF + ELAM, n = 7) or vehicle (normal saline control, HF‐CON, n = 7). After 3 months of therapy, triceps skeletal muscle samples were obtained from all dogs, and the proportion of type 1 and type 2 fibres was assessed. Mitochondria isolated from myofibrils of the vastus lateralis skeletal muscle exposed in vitro to ELAM for 1 h were used to assess mitochondrial function. The proportion of skeletal muscle type 1 fibres was lower in HF‐CON dogs compared with normal dogs (23 ± 4 vs. 32 ± 5%, P < 0.05). Treatment with ELAM restored a near‐normal fibre‐type composition (31 ± 7%, P < 0.05 vs. HF‐CON). Skeletal muscle mitochondria showed significantly lower levels of adenosine diphosphate‐dependent mitochondrial respiration (100 ± 9 vs. 164 ± 15 natom O/min/mg protein, P < 0.05), mitochondrial membrane potential (0.17 ± 0.03 vs. 0.53 ± 0.03 red/green fluorescence ratio, P < 0.05), mitochondrial permeability transition pore (38 ± 3 vs. 62 ± 2 relative light units, P < 0.05), maximum rate of adenosine triphosphate synthesis (3284 ± 418 vs. 8835 ± 423 RLU/μg protein, P < 0.05), and cytochrome c oxidase activity (1390 ± 108 vs. 2459 ± 210 natom O/min/mg protein, P < 0.05) compared with normal dogs. Exposure of skeletal muscle myofibrillar mitochondria from HF dogs to ELAM showed a dose‐dependent improvement/normalization of all measures of mitochondrial function. In mitochondria from skeletal muscle of HF dogs exposed to 0.10 μM ELAM, adenosine diphosphate‐dependent mitochondrial respiration increased to 183 ± 18 natom O/min/mg protein, membrane potential increased to 0.30 ± 0.03 red/green fluorescence ratio, mitochondrial permeability transition pore increased to 54 ± 4 RLU, maximum rate of adenosine triphosphate synthesis increased to 4423 ± 414, and cytochrome c oxidase activity increased to 2033 ± 191 natom O/min/mg protein. Exposure of skeletal muscle myofibrillar mitochondria from normal dogs to ELAM had no effect on mitochondrial function parameters. Conclusions The results indicate that ELAM, previously shown to positively influence mitochondrial function of ...

show abstract

Abnormal Mitochondrial Respiration in Failed Human Myocardium

Cited by 179 publications

References 34 publications

Mitochondria in the human heart

Mitochondria in the human heart

Mitochondrial Biogenesis in Heart: Way of Nurturing and Failure

Effects of elamipretide on skeletal muscle in dogs with experimentally induced heart failure

Contact Info

Product

Resources

About