Metabolomic Analysis in Heart Failure

Abstract

10 s, resulting in the cycling of approximately 6 kg of ATP daily, and the heart displays metabolic flexibility to meet this extremely high demand for energy. 8 Under normal conditions, more than 95% of the ATP consumed in the heart is generated by oxidative phosphorylation, while glycolysis is responsible for approximately 5% and the tricarboxylic acid (TCA) cycle for the remainder. Metabolism of fatty acids generates 70-90% of the ATP required by the heart, with the rest being produced by oxidation of glucose, lactate, ketone bodies, and amino acids. 9 It is well known that utilization of fatty acids is reduced in the failing heart and there is a metabolic shift to generation of ATP from glucose. Such metabolic remodeling is considered to be reasonable because HF is associated with hypoxia and ATP generation per oxygen atom is more efficient when glucose is consumed, compared with fatty acids. 9 In patients with advanced HF, the heart is unable to utilize either metabolite and thus "runs out of fuel". 10 It is reported that the ATP level is approximately 30% lower in failing human hearts compared with non-failing hearts. 11 In addition to this classical premise about the metabolic profile of the failing heart, recent advances in the field of metabolomics have indicated that several metabolites and/or metabolic pathways have a role in HF, as described next. LipidsUnder physiological conditions, the heart mainly generates ATP from fatty acids, but this process declines with progression of HF. Under left ventricular (LV) pressure overload, excessive lipolysis occurs in visceral fat because of increased adrenergic signaling, and this leads to high circulating levels of free fatty acids (FFAs). 12 The serum I t is thought that at least 6,500 low-molecular-weight metabolites exist in humans, and these metabolites have various important roles in biological systems in addition to proteins and genes. 1 Comprehensive assessment of endogenous metabolites is called metabolomics, and recent advances in this field have enabled us to understand the critical role of previously unknown metabolites or metabolic pathways in the maintenance of homeostasis under both physiological and stress conditions. Techniques of metabolomic analysis have been elegantly reported and reviewed elsewhere, 2-4 so the details will not be repeated here. Instead, we will describe the metabolites/metabolic pathways that have been characterized using these techniques and analyzed to improve understanding of various physiological and pathological processes in the field of cardiology. In particular, we will focus on heart failure (HF) and how metabolomic analysis has contributed for improving our understanding of the pathogenesis of this critical condition. Cardiac MetabolismThe number of patients with HF continues to increase and this condition has become a major healthcare issue in many countries. Because the prognosis of severe HF is poor, there are many unmet medical needs for these patients, 5, 6 The pathogenesis of HF is complex and a simple approa...

Injectable Hydrogels for Cardiac Tissue Engineering

“…The infarcted region initially becomes particularly damaged by the ischemic event, then post MI, the surrounding heart wall becomes thinner, leading to ventricular dilation and progression towards HF . During HF, cardiomyocyte (CM) loss, cardiac matrix degradation, and fibrosis make the heart muscle unable to efficiently pump blood to the rest of the body . HF is associated with poor quality of life, high healthcare costs, and a high mortality rate .…”

Combined detection of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 for screening of early heart failure diseases

“…Heart failure is not an independent disease but the end stage of the development of heart diseases. Although the trend of younger heart failure group rises substantial in recent years, no enough research attention has been paid to the younger generation [1][2][3][4][5]. Therefore, effective diagnosis and prevention of heart failure is an urgent problem in medical and biological researches [6][7][8][9].…”

PET imaging of glucose and fatty acid metabolism for NAFLD patients

“…The paper presented in this issue of the Journal by Tang and colleagues illuminate the deficiency in our knowledge of the reciprocal metabolic relationship between liver and heart in health and disease. 1 The results presented in this paper used a large number of previously acquired 18 F-FDG PET studies to investigate the association between non-alcoholic fatty liver disease (NAFLD) ( Figure 1A) and myocardial glucose uptake. Previous work published by Lee and colleagues in Metabolism, 2 had found a significant correlation between NAFLD and vascular inflammation using 18 F-FDG PET to measure maximum target-to-background uptake in the carotid arteries; however, the present study is the first to elicit through imaging the correlation between NAFLD and potential cardiac metabolic abnormalities.…”

“…3 It has been pointed out that the leading cause of death in NAFLD patients is CVD rather than liver-associated complications, 4 of which only 5% of NAFLD patients die from liver-related diseases. 5 18 F-FGD PET is an important indicator of cardiac glucose metabolism and its alteration in the presence of disease; however, to systematically understand the relation between NAFLD and the risk of cardiovascular disease, other probes, in addition to 18 FDG, should be used to study the complex and dynamic pathways of energy substrate metabolism in the heart in health and disease and their relationship to the metabolic pathways of other body organs.…”

“…The aim of the paper by Tang and colleagues was to investigate the association between NAFLD and myocardial glucose uptake to see if alterations in 18 F-FDG uptake could be an indicator of cardiac dysfunction in NAFLD individuals. They retrospectively assessed 18 F-FDG PET imaging data of a total of 201 subjects with NAFLD and 542 without NAFLD who were imaged over the years from December 1, 2011 to November 30, 2017. The liver ( Figure 1B) in addition to adipose tissue is a major source of lipoproteins (Figure 1C), which are a major substrate for cardiac ATP production.…”