Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials

Bhatt, Kunal; Butler, Javed

doi:10.1007/s11897-018-0386-8

Cited by 14 publications

(10 citation statements)

References 54 publications

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“…Heart failure (HF) is a global disease, which is a consequence of the aging world population. HF is a common cause of hospitalization for patients over 65 years of age and is predicted to cause a heavy financial burden on health care worldwide (Bhatt & Butler, 2018).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Hsieh

Hsu

et al. 2019

British J Pharmacology

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Background and PurposeMitochondrial dysfunction plays a role in the progression of cardiovascular diseases including heart failure. 3‐Hydroxy‐3‐methylglutaryl‐CoA reductase inhibitors (statins), which inhibit ROS synthesis, show cardioprotective effects in chronic heart failure. However, the beneficial role of statins in mitochondrial protection in heart failure remains unclear.Experimental ApproachRats were treated with angiotensin II (1.5 mg·kg−1·day−1) or co‐administered simvastatin (oral, 10 mg·kg−1) for 14 days; and then administration was stopped for the following 14 days. Cardiac structure/function was examined by wheat germ agglutinin staining and echocardiography. Mitochondrial morphology and the numbers of lipid droplets, lysosomes, autophagosomes, and mitophagosomes were determined by transmission electron microscopy. Human cardiomyocytes were stimulated, and intracellular ROS and mitochondrial membrane potential (ΔΨ m) changes were measured by flow cytometry and JC‐1 staining, respectively. Autophagy and mitophagy‐related and mitochondria‐regulated apoptotic proteins were identified by immunohistochemistry and western blotting.Key ResultsSimvastatin significantly reduced ROS production and attenuated the disruption of ΔΨ m. Simvastatin induced the accumulation of lipid droplets to provide energy for maintaining mitochondrial function, promoted autophagy and mitophagy, and inhibited mitochondria‐mediated apoptosis. These findings suggest that mitochondrial protection mediated by simvastatin plays a therapeutic role in heart failure prevention by modulating antioxidant status and promoting energy supplies for autophagy and mitophagy to inhibit mitochondrial damage and cardiomyocyte apoptosis.Conclusion and ImplicationsMitochondria play a key role in mediating heart failure progression. Simvastatin attenuated heart failure, induced by angiotensin II, via mitochondrial protection and might provide a new therapy to prevent heart failure.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Hsieh

Hsu

et al. 2019

British J Pharmacology

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“…However, whether these can also be implicated in immune-related functions is still not known. For example, coenzyme Q10 in mitochondria can be utilized as a potential treatment for heart failure ( 144 ). Genipin is a UCP2 inhibitor that is useful for anticancer therapy ( 145 ).…”

Section: Does Mitochondrial Immune Regulation Have Any Therapeutic Immentioning

confidence: 99%

Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism

et al. 2018

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Lack of immune system cells or impairment in differentiation of immune cells is the basis for many chronic diseases. Metabolic changes could be the root cause for this immune cell impairment. These changes could be a result of altered transcription, cytokine production from surrounding cells, and changes in metabolic pathways. Immunity and mitochondria are interlinked with each other. An important feature of mitochondria is it can regulate activation, differentiation, and survival of immune cells. In addition, it can also release signals such as mitochondrial DNA (mtDNA) and mitochondrial ROS (mtROS) to regulate transcription of immune cells. From current literature, we found that mitochondria can regulate immunity in different ways. First, alterations in metabolic pathways (TCA cycle, oxidative phosphorylation, and FAO) and mitochondria induced transcriptional changes can lead to entirely different outcomes in immune cells. For example, M1 macrophages exhibit a broken TCA cycle and have a pro-inflammatory role. By contrast, M2 macrophages undergo β-oxidation to produce anti-inflammatory responses. In addition, amino acid metabolism, especially arginine, glutamine, serine, glycine, and tryptophan, is critical for T cell differentiation and macrophage polarization. Second, mitochondria can activate the inflammatory response. For instance, mitochondrial antiviral signaling and NLRP3 can be activated by mitochondria. Third, mitochondrial mass and mobility can be influenced by fission and fusion. Fission and fusion can influence immune functions. Finally, mitochondria are placed near the endoplasmic reticulum (ER) in immune cells. Therefore, mitochondria and ER junction signaling can also influence immune cell metabolism. Mitochondrial machinery such as metabolic pathways, amino acid metabolism, antioxidant systems, mitochondrial dynamics, mtDNA, mitophagy, and mtROS are crucial for immune functions. Here, we have demonstrated how mitochondria coordinate to alter immune responses and how changes in mitochondrial machinery contribute to alterations in immune responses. A better understanding of the molecular components of mitochondria is necessary. This can help in the development of safe and effective immune therapy or prevention of chronic diseases. In this review, we have presented an updated prospective of the mitochondrial machinery that drives various immune responses.

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“…Adequate ATP is important for cellular function, and ATP deficiency is associated with numerous diseases including impaired cardiac function leading to congestive heart failure [ 11 ]. Brain tissue function is dependent on ATP, and ATP deficiency impacts the occurrence and clinical course of diseases such obstructive sleep apnea [ 12 ] and Alzheimer's disease [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a point-of-contact technique to measure adenosine triphosphate: A quality improvement study

Pierce

Hiebert

Mahoney

et al. 2019

Annals of Medicine and Surgery

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Purpose Patients with heart failure with preserved ejection fraction (HFpEF) experience fatigue due to impaired myocardial bioenergetics. Cardiomyocyte function depends on the delivery of adenosine triphosphate (ATP), yet there is no convenient bedside method to measure ATP. The purpose of this study was to develop a point-of-contact measurement of ATP that can be used in a clinical setting. Methods In a laboratory setting, digital finger punctures were conducted using 5 μl and 10 μl of capillary blood placed into various amounts of water (H2O). After mixing the solution for 10 s, a Hygiena AquaSnapTM Free ATP probe was placed into the solution for 10 s for the detection of ATP. The probe was then placed into the Hygiena luminometer for 15 s, and a value in relative light units (RLU) was obtained. Results Test samples using 10 μl of blood diluted from 50 to 500 mls of H2O produced ATP readings of 10,000-7569 RLUs. Using 5 μl of blood in 375–900 ml of H2O decreased the ATP values to 6459-4189 RLUs. Dilutional volume sparing experiments were conducted with ATP standards to determine the concentration of ATP per RLUs. Conclusion Patients with HFpEF have increased metabolic demand and impaired myocardial bioenergetics. Thus, identifying a method to measure ATP that is quick and accurate is imperative to accurately assess cellular energy production in this population. Point-of-contact measures, such as ATP, are needed for precision-guided treatment. Data from this study provides the first step toward developing evidence for health policies related to managing fatigue.

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Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials

Cited by 14 publications

References 54 publications

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Mitochondrial protection by simvastatin against angiotensin II‐mediated heart failure

Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism

Development of a point-of-contact technique to measure adenosine triphosphate: A quality improvement study

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