The different effects of leucine, isoleucine, and valine on systolic properties of the normal and septic isolated rat heart

Markovitz, Lawrence J.; Hasin, Yonathan; Dann, Eldad J.; Gotsman, Mervyn S.; Freund, Herbert R.

doi:10.1016/0022-4804(85)90031-9

Cited by 5 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Benefits from the use of branched-chain amino acids in isolated normal and septic hearts have long been recognized 25,26. Intriguingly, we found that the E2 subunit of branched-chain α -keto acid dehydrogenase was increased in CRT compared with DHF.…”

Section: Discussionmentioning

confidence: 63%

Modulation of Mitochondrial Proteome and Improved Mitochondrial Function by Biventricular Pacing of Dyssynchronous Failing Hearts

Agnetti

Kaludercic

Kane

et al. 2010

Circ Cardiovasc Genet

103

View full text Add to dashboard Cite

Background-Cardiac resynchronization therapy (CRT) improves chamber mechanoenergetics and morbidity and mortality of patients manifesting heart failure with ventricular dyssynchrony; however, little is known about the molecular changes underlying CRT benefits. We hypothesized that mitochondria may play an important role because of their involvement in energy production. Methods and Results-Mitochondria isolated from the left ventricle in a canine model of dyssynchronous or resynchronized (CRT) heart failure were analyzed by a classical, gel-based, proteomic approach. Two-dimensional gel electrophoresis revealed that 31 mitochondrial proteins where changed when controlling the false discovery rate at 30%. Key enzymes in anaplerotic pathways, such as pyruvate carboxylation and branched-chain amino acid oxidation, were increased. These concerted changes, along with others, suggested that CRT may increase the pool of Krebs cycle intermediates and fuel oxidative phosphorylation. Nearly 50% of observed changes pertained to subunits of the respiratory chain. ATP synthase-␤ subunit of complex V was less degraded, and its phosphorylation modulated by CRT was associated with increased formation (2-fold, Pϭ0.004) and specific activity (ϩ20%, Pϭ0.05) of the mature complex. The importance of these modifications was supported by coordinated changes in mitochondrial chaperones and proteases. CRT increased the mitochondrial respiratory control index with tightened coupling when isolated mitochondria were reexposed to substrates for both complex I (glutamate and malate) and complex II (succinate), an effect likely related to ATP synthase subunit modifications and complex quantity and activity. Conclusions-CRT potently affects both the mitochondrial proteome and the performance associated with improved cardiac function. (Circ Cardiovasc Genet. 2010;3:78-87.)Key Words: cardiac resynchronization therapy Ⅲ mitochondria Ⅲ proteomics Ⅲ ATP synthase H eart failure (HF) is a leading cause of morbidity and mortality in older adults, affecting 5 million individuals in the US alone. 1 A subset of patients with HF also develops regional conduction delay, resulting in discoordinate contraction that worsens symptoms and ultimate prognosis. Since the turn of the millennium, cardiac resynchronization therapy (CRT), also referred to as biventricular pacing, has become a clinical treatment for such patients, improving heart function, clinical symptoms, and survival. 2,3 Some recent studies 4 -6 have revealed changes in gene expression and molecular remodeling of stress response kinases and cell survival signaling associated with CRT. Among the earliest findings in clinical CRT studies was the demonstration that CRT improves chamber energetic efficiency. This effect is rapid, resulting from the retiming of contraction to synchronously occur in both sides of the myocardium, reducing wasted chamber work much like tuning a car engine. Given the importance of abnormal mechanoenergetics in HF and centrality of ATP cycling, 7 we hypothesized that CR...

show abstract

Section: Discussionmentioning

confidence: 63%

Modulation of Mitochondrial Proteome and Improved Mitochondrial Function by Biventricular Pacing of Dyssynchronous Failing Hearts

Agnetti

Kaludercic

Kane

et al. 2010

Circ Cardiovasc Genet

103

View full text Add to dashboard Cite

show abstract

“…Oral BCAA supplementation promoted mitochondrial biogenesis of the heart and skeletal muscles through eNOS-derived nitric oxide, decreased ROS in cardiac and skeletal muscles, and prolonged the survival of mice [11]. A leucine diet attenuated myocardial infarction in mice accompanied by a significant increase in cardiac ATP content [17], and leucine and isoleucine improved cardiac systolic function in septic isolated rat heart [48].…”

Section: Discussionmentioning

confidence: 98%

Branched-chain amino acids ameliorate heart failure with cardiac cachexia in rats

et al. 2015

View full text Add to dashboard Cite

show abstract

“…High levels of both extracellular and intracellular BCAAs could be detrimental to cardiac function. Perfusion of rat hearts with relatively high levels of leucine and isoleucine causes systolic dysfunction 291 and has a general cardiodepressant effect. 292 Excessive levels of BCAAs and their catabolites inhibit the activities of α-ketoglutarate and pyruvate dehydrogenases and mitochondrial respiration.…”

Section: Role Of Metabolism In Pathological Cardiac Remodelingmentioning

confidence: 99%

Metabolic Coordination of Physiological and Pathological Cardiac Remodeling

Gibb

Hill

2018

Circulation Research

275

232

View full text Add to dashboard Cite

Metabolic pathways integrate to support tissue homeostasis and to prompt changes in cell phenotype. In particular, the heart consumes relatively large amounts of substrate not only to regenerate ATP for contraction but also to sustain biosynthetic reactions for replacement of cellular building blocks. Metabolic pathways also control intracellular redox state, and metabolic intermediates and end products provide signals that prompt changes in enzymatic activity and gene expression. Mounting evidence suggests that the changes in cardiac metabolism that occur during development, exercise, and pregnancy as well as with pathological stress (eg, myocardial infarction, pressure overload) are causative in cardiac remodeling. Metabolism-mediated changes in gene expression, metabolite signaling, and the channeling of glucose-derived carbon toward anabolic pathways seem critical for physiological growth of the heart, and metabolic inefficiency and loss of coordinated anabolic activity are emerging as proximal causes of pathological remodeling. This review integrates knowledge of different forms of cardiac remodeling to develop general models of how relationships between catabolic and anabolic glucose metabolism may fortify cardiac health or promote (mal)adaptive myocardial remodeling. Adoption of conceptual frameworks based in relational biology may enable further understanding of how metabolism regulates cardiac structure and function.

show abstract

The different effects of leucine, isoleucine, and valine on systolic properties of the normal and septic isolated rat heart

Cited by 5 publications

References 14 publications

Modulation of Mitochondrial Proteome and Improved Mitochondrial Function by Biventricular Pacing of Dyssynchronous Failing Hearts

Modulation of Mitochondrial Proteome and Improved Mitochondrial Function by Biventricular Pacing of Dyssynchronous Failing Hearts

Branched-chain amino acids ameliorate heart failure with cardiac cachexia in rats

Metabolic Coordination of Physiological and Pathological Cardiac Remodeling

Contact Info

Product

Resources

About