Stable Isotopes for Tracing Cardiac Metabolism in Diseases

Abstract

Although metabolic remodeling during cardiovascular diseases has been well-recognized for decades, the recent development of analytical platforms and mathematical tools has driven the emergence of assessing cardiac metabolism using tracers. Metabolism is a critical component of cellular functions and adaptation to stress. The pathogenesis of cardiovascular disease involves metabolic adaptation to maintain cardiac contractile function even in advanced disease stages. Stable-isotope tracer measurements are a powerful tool for measuring flux distributions at the whole organism level and assessing metabolic changes at a systems level in vivo. The goal of this review is to summarize techniques and concepts for in vivo or ex vivo stable isotope labeling in cardiovascular research, to highlight mathematical concepts and their limitations, to describe analytical methods at the tissue and single-cell level, and to discuss opportunities to leverage metabolic models to address important mechanistic questions relevant to all patients with cardiovascular disease.

Tracing the path of disruption: 13C isotope applications in traumatic brain injury‐induced metabolic dysfunction

“…While traditional metabolic measurement techniques focus on net substrate concentrations at specific time points, isotope tracing can infer metabolic flux over a defined period, measuring substrate flow through a pathway per unit of time. 116 This technology, proven effective in various models and organ systems, 11 , 12 , 117 , 118 is crucial for characterizing the intricate chemical changes contributing to secondary brain injury (Figure 1 , Tables 2 and 3 ).…”

“…NMR and LC/GC–MS are extensively used analytic techniques in isotope tracing studies in the current literature. 11 , 12 , 13 , 33 , 117 , 118 , 119 , 120 These established techniques provide detailed data on numerous substrates and metabolites in a sample. Recent computing advancements facilitate cross‐referencing metabolite readouts to libraries, aiding in identifying unexpected pathway alterations.…”

“…Signal detection and quantification in isotope tracing relies on various techniques, each with distinct advantages and limitations. NMR and LC/GC–MS are extensively used analytic techniques in isotope tracing studies in the current literature 11–13,33,117–120 . These established techniques provide detailed data on numerous substrates and metabolites in a sample.…”

Intersection of Immunology and Metabolism in Myocardial Disease

“…Additional information on the flux through an enzymatic reaction or network is required to answer this question. Flux analysis encompasses a set of different tools to answer such questions, including tracer-based metabolomics, 12,126,127 measurements of enzymatic activities, or computational modeling [128][129][130] (Figure 3B). The most important tools for flux analysis are tracer-based studies, including stable-isotope tracers of common nutrients or radioactive probes.…”

Ectonucleotidases as bridge between the ATP and adenosine world: reflections on Geoffrey Burnstock

“…Given the complexities of extracellular purine metabolism, future studies on the dynamics of this pathway might involve the application of isotopically labelled tracers combined with NMR and mass spectrometry, techniques that were successfully applied in the past to metabolic pathways in various organs [ 36 ]. Challenges persist as to the accurate estimation of substrate concentrations and flux rates from stable-isotope tracers.…”