Cardiac Energy Metabolism in Heart Failure

Circulation Research, Год журнала: 2021, Номер 128(10), С. 1487 - 1513

Опубликована: Май 13, 2021

Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, metabolic changes that occur failure are complex and dependent not only on type present but also co-existence common comorbidities such as obesity 2 diabetes. The failing faces an deficit, primarily because a decrease mitochondrial oxidative capacity. This is partly compensated for by increase ATP production from glycolysis. relative contribution different fuels changes, including glucose amino acid oxidation, ketone oxidation. oxidation fatty acids increases or decreases, depending For instance, associated with diabetes obesity, myocardial increases, while hypertension ischemia, decreases. Combined, these result becoming less efficient (ie, work/O consumed). alterations both glycolysis due transcriptional key enzymes involved pathways, well NAD redox state (NAD + nicotinamide adenine dinucleotide levels) metabolite signaling posttranslational epigenetic control expression genes encoding enzymes. fate glucose, beyond flux through pathology Of importance, pharmacological targeting pathways has emerged novel therapeutic approach improving efficiency, decreasing deficit function heart.

Язык: Английский

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Epigenetic regulation of aging: implications for interventions of aging and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Ноя. 7, 2022

Abstract Aging is accompanied by the decline of organismal functions and a series prominent hallmarks, including genetic epigenetic alterations. These aging-associated changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, all which participate in regulation aging process, hence contribute to aging-related diseases. Therefore, understanding mechanisms will provide new avenues develop strategies delay aging. Indeed, interventions based on manipulating have led alleviation or extension lifespan animal models. Small molecule-based therapies reprogramming that enable rejuvenation been developed for ameliorating reversing conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, calibrating circadian rhythm, has demonstrated Furthermore, various clinical trials intervention are ongoing, providing more evidence safety efficacy these therapies. Here, we review recent work outline advances age-associated A better critical roles epigenetics process lead prevention human therapy

Язык: Английский

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Mitochondrial dysfunction: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Язык: Английский

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NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Сен. 16, 2021

Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD

Язык: Английский

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Nicotinamide for the treatment of heart failure with preserved ejection fraction

Science Translational Medicine, Год журнала: 2021, Номер 13(580)

Опубликована: Фев. 10, 2021

The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.

Язык: Английский

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Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges

Nature Reviews Cardiology, Год журнала: 2023, Номер 20(12), С. 812 - 829

Опубликована: Май 26, 2023

Язык: Английский

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Critical Role of the cGAS-STING Pathway in Doxorubicin-Induced Cardiotoxicity

Circulation Research, Год журнала: 2023, Номер 132(11)

Опубликована: Май 8, 2023

Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator interferon genes) pathway plays a critical role in cardiovascular destruction. Here, we investigate involvement this mechanism doxorubicin-induced (DIC). Mice were treated with low-dose doxorubicin to induce chronic DIC. The cGAS-STING DIC was evaluated cGAS-deficiency (cGAS-/-), Sting-deficiency (Sting-/-), and regulatory factor 3 (Irf3)-deficiency (Irf3-/-) mice. Endothelial cell (EC)-specific conditional Sting deficiency (Stingflox/flox/Cdh5-CreERT) mice used assess importance ECs during We also examined direct effects on nicotinamide adenine dinucleotide (NAD) homeostasis vitro vivo. In model, observed significant cardiac ECs. Global cGAS, Sting, Irf3 all markedly ameliorated EC-specific significantly prevented endothelial dysfunction. Mechanistically, activated EC target, IRF3, which directly induced CD38 expression. ECs, caused reduction NAD levels subsequent mitochondrial dysfunction via intracellular glycohydrolase (NADase) activity CD38. Furthermore, regulates bioenergetics cardiomyocytes through ecto-NADase demonstrated pharmacological inhibition TANK-binding kinase 1 or effectively without compromising anticancer doxorubicin. Our findings indicate may represent novel therapeutic target preventing

Язык: Английский

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Deranged Myocardial Fatty Acid Metabolism in Heart Failure

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 996 - 996

Опубликована: Янв. 17, 2022

The heart requires fatty acids to maintain its activity. Various mechanisms regulate myocardial acid metabolism, such as energy production using fuel, for which it is known that coordinated control of uptake, β-oxidation, and mitochondrial oxidative phosphorylation steps are important efficient adenosine triphosphate (ATP) without unwanted side effects. taken up by cardiomyocytes not only used substrates but also the synthesis triglycerides replacement reaction chains in cell membrane phospholipids. Alterations metabolism affect structure function heart. Recently, breakthrough studies have focused on key transcription factors signaling systems modify their functions. In this article, we reviewed latest research role pathogenesis failure provide an outlook future challenges.

Язык: Английский

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Therapeutic application of natural products: NAD+ metabolism as potential target

Phytomedicine, Год журнала: 2023, Номер 114, С. 154768 - 154768

Опубликована: Март 13, 2023

Язык: Английский

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Inflammation in Myocardial Ischemia/Reperfusion Injury: Underlying Mechanisms and Therapeutic Potential

Antioxidants, Год журнала: 2023, Номер 12(11), С. 1944 - 1944

Опубликована: Окт. 31, 2023

Acute myocardial infarction (MI) occurs when blood flow to the myocardium is restricted, leading cardiac damage and massive loss of viable cardiomyocytes. Timely restoration coronary considered gold standard treatment for MI patients limits infarct size; however, this intervention, known as reperfusion, initiates a complex pathological process that somewhat paradoxically also contributes injury. Despite being sterile environment, ischemia/reperfusion (I/R) injury triggers inflammation, which expansion subsequent remodeling wound healing. The immune response comprised subsets both myeloid lymphoid-derived cells act in concert modulate pathogenesis resolution I/R Multiple mechanisms, including altered metabolic status, regulate cell activation function setting acute MI, yet our understanding remains incomplete. While numerous studies demonstrated benefit following strategies target inflammation preclinical models, therapeutic attempts mitigate were less successful. Therefore, further investigation leveraging emerging technologies needed better characterize intricate inflammatory elucidate its influence on progression heart failure.

Язык: Английский

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