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Researchers at Oxford are interested in cardiac metabolism, energetics and function and how diabetes, obesity and cardiac failure impact on these.

Anatomy of a human heart on ECG medical background. 3d render

The heart is a metabolically demanding organ. It is put under considerable strain in type 2 diabetes to the extent that heart disease is the leading cause of mortality in these patients. The substrates selected by the heart for generating energy are vital to its function and disease states such as diabetes, obesity and cardiac failure are associated with changes in substrate used. Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques are powerful non-invasive approaches used to study this and are carried out in humans at the Oxford Centre for Clinical Magnetic Resonance Research and in rodent models. 

Oxford has pioneered the use of hyperpolarized 13C magnetic resonance spectroscopy and imaging to visualise in real-time the rates of key metabolic pathways in organs. The approach is being used to study alterations in metabolism in the diabetic heart and other organs, including the metabolic interactions between multiple organs such as the heart and liver, and to explore the effects of anti-diabetic medications, with the aim of transforming how we detect and treat cardiac disease. Changes in the metabolic behaviour of cardiac cells are also important during development, and researchers are exploring how to manipulate cardiac progenitor cells to improve their metabolic flexibility and potential therapeutic value.

Other studies at Oxford include exploring how metabolic changes that give rise to diabetes, insulin resistance or obesity affect the cardiovascular system via changes in adipose tissue biology. This crosstalk between adipose tissue and the cardiovascular system in cardiovascular disease is studied using a range of genetic, cellular and imaging approaches. The bioresource Ox-HVF, a cohort that includes more than 1500 patients undergoing cardiac surgery from whom samples of cardiovascular and adipose tissue are harvested during surgery, is particularly valuable for this work.

Researchers are also exploring cardiac metabolism and the contribution of specific metabolic pathways to cardiac function in health and disease using transgenic or clinically relevant mouse models, with the aim of finding new therapeutic tools for heart complications. In addition, there are groups interested in studying how key cell types, including fibroblasts and inflammatory macrophages, may contribute to cardiac disease. Heart disease is a common consequence of iron imbalance and to explore the mechanisms involved, researchers are investigating iron regulation in the heart, as well as in other organs, using mouse models carrying tissue-specific alterations in iron metabolism. 

Prospective cohorts such as the Mexico City Prospective Study, the China Kadoorie Biobank Study and UK Biobank enable researchers to explore the interplay between lifestyle, genetic and environmental factors and the risk of cardiovascular disease across different populations. 

The Cardiovascular theme within the Oxford NIHR Biomedical Research Centre supports clinical research in many of these areas. In addition, the entire cardiovascular research spectrum, from discovery science through to clinical and population health research, is covered by the Oxford British Heart Foundation Centre for Research Excellence (Oxford BHF CRE).