Stable Isotopes for Tracing Cardiac Metabolism in Diseases

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.