scholarly journals The Role of Metabolism in Heart Failure and Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Jiyoung Bae ◽  
Wyatt G. Paltzer ◽  
Ahmed I. Mahmoud
Keyword(s):  
Heart Failure ◽  
Cell Fate ◽  
Therapeutic Potential ◽  
Systolic Heart Failure ◽  
Cardiac Metabolism ◽  
Mitochondrial Metabolism ◽  
Acid Oxidation ◽  
Adult Heart ◽  
Mammalian Heart

Heart failure is the leading cause of death worldwide. The inability of the adult mammalian heart to regenerate following injury results in the development of systolic heart failure. Thus, identifying novel approaches toward regenerating the adult heart has enormous therapeutic potential for adult heart failure. Mitochondrial metabolism is an essential homeostatic process for maintaining growth and survival. The emerging role of mitochondrial metabolism in controlling cell fate and function is beginning to be appreciated. Recent evidence suggests that metabolism controls biological processes including cell proliferation and differentiation, which has profound implications during development and regeneration. The regenerative potential of the mammalian heart is lost by the first week of postnatal development when cardiomyocytes exit the cell cycle and become terminally differentiated. This inability to regenerate following injury is correlated with the metabolic shift from glycolysis to fatty acid oxidation that occurs during heart maturation in the postnatal heart. Thus, understanding the mechanisms that regulate cardiac metabolism is key to unlocking metabolic interventions during development, disease, and regeneration. In this review, we will focus on the emerging role of metabolism in cardiac development and regeneration and discuss the potential of targeting metabolism for treatment of heart failure.

P1665Identifying metabolic treatment strategies for heart failure - A meta-analytic approach

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T D Nguyen ◽  
C Schenkl ◽  
P Schlattmann ◽  
E Heyne ◽  
T Doenst ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Publication Bias ◽  
Treatment Strategies ◽  
Cardiac Metabolism ◽  
Acid Oxidation ◽  
Beneficial Result ◽  
Study Characteristics ◽  
Metabolic Treatment

Abstract Background Current expert consensus suggests modulation of cardiac glucose oxidation (GO) or fatty acid oxidation (FAO) as a therapeutic approach for heart failure (HF). However, inconsistency exists and there is no systematic evidence supporting this concept. Objective We conducted a systematic review of preclinical studies to assess the role of metabolic treatment in HF. We aimed to identify, via meta-analytic techniques, specific metabolic strategies that potentially improve cardiac function. Methods We searched PubMed, Web of Science and reference lists of identified primary studies from inception to 31 December 2018. We included all interventional studies that assessed changes in cardiac function together with those in cardiac GO and/or FAO in established animal models of HF. Two investigators extracted study characteristics and data independently. We encompassed all available measures of cardiac function in the analysis instead of selecting one single outcome. Effect sizes were calculated as Hedges' g. We used I2 to estimate heterogeneity, metaregression to explore sources of heterogeneity and contour-enhanced funnel plot to assess publication bias. Results Our search returned 64 reports that fulfilled the inclusion criteria (n=1532 animals). The overall effect of treatments associated with metabolic changes was 0.78±0.16 g, p<0.001. There was a high heterogeneity (I2 = 86.7%) and no signs of publication bias. Metaregression revealed that treatments associated with an increase in GO (1.09±0.13 g, p<0.001) markedly enhance cardiac function. In contrast, those associated with decreased GO may worsen outcome. Although most experts suggest inhibiting FAO to improve cardiac function in HF, we found a beneficial result with a large total effect size for approaches that boost FAO (1.69±0.65 g, p<0.01). Conclusions Our data highlight the role of cardiac metabolism in treating HF. Specifically, increasing GO or FAO may considerably improve cardiac function. Furthermore, the findings challenge the common notion that inhibiting cardiac FAO is protective.

scholarly journals Metabolic Therapy in Heart Failure

2015 ◽  
Vol 1 (2) ◽  
pp. 112 ◽  
Author(s):  
Yury Lopatin ◽  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Glucose Oxidation ◽  
Acid Oxidation ◽  
Patients With Heart Failure ◽  
Cardiac Energy Metabolism ◽  
Conventional Medical Therapy ◽  
Cardiac Energy ◽  
Metabolic Impairments

Metabolic impairments play an important role in the development and progression of heart failure. The use of metabolic modulators, the number of which is steadily increasing, may be particularly effective in the treatment of heart failure. Recent evidence suggests that modulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation represents a promising approach to the treatment of patients with heart failure. This review focuses on the role of metabolic modulators, in particular trimetazidine, as a potential additional medication to conventional medical therapy in heart failure.

scholarly journals Metabolic inflammation in heart failure with preserved ejection fraction

2020 ◽  
Author(s):  
Gabriele G Schiattarella ◽  
Daniele Rodolico ◽  
Joseph A Hill
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Metabolism ◽  
Biological Processes ◽  
Preserved Ejection Fraction ◽  
Metabolic Inflammation ◽  
Treatment And Prevention ◽  
Metabolic Comorbidities ◽  
Inflammatory Burden

Abstract One in 10 persons in the world aged 40 years and older will develop the syndrome of HFpEF (heart failure with preserved ejection fraction), the most common form of chronic cardiovascular disease for which no effective therapies are currently available. Metabolic disturbance and inflammatory burden contribute importantly to HFpEF pathogenesis. The interplay within these two biological processes is complex; indeed, it is now becoming clear that the notion of metabolic inflammation—metainflammation—must be considered central to HFpEF pathophysiology. Inflammation and metabolism interact over the course of syndrome progression, and likely impact HFpEF treatment and prevention. Here, we discuss evidence in support of a causal, mechanistic role of metainflammation in shaping HFpEF, proposing a framework in which metabolic comorbidities profoundly impact cardiac metabolism and inflammatory pathways in the syndrome.

scholarly journals Mending a broken heart: the role of mitophagy in cardioprotection

2015 ◽  
Vol 308 (3) ◽  
pp. H183-H192 ◽  
Author(s):  
Alexandra G. Moyzis ◽  
Junichi Sadoshima ◽  
Åsa B. Gustafsson
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Cellular Processes ◽  
Differentiated Cells ◽  
Calcium Storage ◽  
Response To Stress ◽  
Metabolite Synthesis ◽  
Energy Dependent

The heart is highly energy dependent with most of its energy provided by mitochondrial oxidative phosphorylation. Mitochondria also play a role in many other essential cellular processes including metabolite synthesis and calcium storage. Therefore, maintaining a functional population of mitochondria is critical for cardiac function. Efficient degradation and replacement of dysfunctional mitochondria ensures cell survival, particularly in terminally differentiated cells such as cardiac myocytes. Mitochondria are eliminated via mitochondrial autophagy or mitophagy. In the heart, mitophagy is an essential housekeeping process and required for cardiac homeostasis. Reduced autophagy and accumulation of impaired mitochondria have been linked to progression of heart failure and aging. In this review, we discuss the pathways that regulate mitophagy in cells and highlight the cardioprotective role of mitophagy in response to stress and aging. We also discuss the therapeutic potential of targeting mitophagy and directions for future investigation.

scholarly journals Modulation of Cardiac Metabolism in Heart Failure

2019 ◽  
Vol 17 ◽  
Author(s):  
Giuseppe Rosano ◽  
Andrew Coats
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Skeletal Muscles ◽  
Cardiac Metabolism ◽  
Acid Oxidation ◽  
Patients With Heart Failure ◽  
Free Fatty Acid Oxidation ◽  
Capacity Modulation

Heart failure is associated with altered cardiac metabolism, in part, due to maladaptive mechanisms, in part secondary to comorbidities such as diabetes and ischaemic heart disease. The metabolic derangements taking place in heart failure are not limited to the cardiac myocytes, but extend to skeletal muscles and the vasculature causing changes that contribute to the worsening of exercise capacity. Modulation of cardiac metabolism with partial inhibition of free fatty acid oxidation has been shown to be beneficial in patients with heart failure. At the present, the bulk of evidence for this class of drugs comes from Trimetazidine. Newer compounds partially inhibiting free fatty acid oxidation or facilitating the electron transport on the mitochondrial cristae are in early phase of their clinical development.

scholarly journals PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity

2010 ◽  
Vol 299 (2) ◽  
pp. E145-E161 ◽  
Author(s):  
Vitor A. Lira ◽  
Carley R. Benton ◽  
Zhen Yan ◽  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Transgenic Mice ◽  
Mitochondrial Biogenesis ◽  
Therapeutic Potential ◽  
Fiber Type ◽  
Acid Oxidation ◽  
Physiological Limits ◽  
Exercise Induced

The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is a major regulator of exercise-induced phenotypic adaptation and substrate utilization. We provide an overview of 1) the role of PGC-1α in exercise-mediated muscle adaptation and 2) the possible insulin-sensitizing role of PGC-1α. To these ends, the following questions are addressed. 1) How is PGC-1α regulated, 2) what adaptations are indeed dependent on PGC-1α action, 3) is PGC-1α altered in insulin resistance, and 4) are PGC-1α-knockout and -transgenic mice suitable models for examining therapeutic potential of this coactivator? In skeletal muscle, an orchestrated signaling network, including Ca2+-dependent pathways, reactive oxygen species (ROS), nitric oxide (NO), AMP-dependent protein kinase (AMPK), and p38 MAPK, is involved in the control of contractile protein expression, angiogenesis, mitochondrial biogenesis, and other adaptations. However, the p38γ MAPK/PGC-1α regulatory axis has been confirmed to be required for exercise-induced angiogenesis and mitochondrial biogenesis but not for fiber type transformation. With respect to a potential insulin-sensitizing role of PGC-1α, human studies on type 2 diabetes suggest that PGC-1α and its target genes are only modestly downregulated (≤34%). However, studies in PGC-1α-knockout or PGC-1α-transgenic mice have provided unexpected anomalies, which appear to suggest that PGC-1α does not have an insulin-sensitizing role. In contrast, a modest (∼25%) upregulation of PGC-1α, within physiological limits, does improve mitochondrial biogenesis, fatty acid oxidation, and insulin sensitivity in healthy and insulin-resistant skeletal muscle. Taken altogether, there is substantial evidence that the p38γ MAPK-PGC-1α regulatory axis is critical for exercise-induced metabolic adaptations in skeletal muscle, and strategies that upregulate PGC-1α, within physiological limits, have revealed its insulin-sensitizing effects.

Sign in / Sign up

Export Citation Format

Share Document