Antoniades Group - Cross-talk between adipose tissue and the cardiovascular system in humans: From novel imaging biomarkers development to drug target discovery

Adipose tissue is now considered to be a “biochemical factory” in the human body, producing a wide range of bioactive molecules, such as adipokines. These molecules exert local autocrine effects, but they also have paracrine and endocrine properties, and may play a critical role in the regulation of redox state and signalling in various tissues, such as the vascular wall and myocardium. Our group studies the mechanisms by which different adipose tissue depots in the human body affect vascular and myocardial redox state in atherosclerosis. We also search for novel therapeutic strategies targeting vascular and myocardial redox signalling directly or through changes in the crosstalk between adipose tissue and cardiovascular system.

Our group undertakes translational research, moving from bench to bedside and vice versa. We use various clinical research tools, such as non-invasive imaging and others, for the evaluation of vascular / myocardial function. This includes studies on human tissues; we have developed a number of ex vivo models of human tissue (vessels, myocardium and adipose tissue) for translational research, which are complemented by tissue and cell culture techniques. We have also established a large bioresource of human vascular, myocardial and adipose tissue in collaboration with other academic institutions across the world (The Oxford Heart Vessels & Fat (ox-HVF) cohort) and this is currently being used to support hypothesis driven research in the field of vascular and myocardial redox state regulation.

In our lab state-of-the-art techniques are used to visualise and quantify vascular and myocardial free radical production.

Using genetic tools to identify patients with pre-specified genetic traits, enables us to apply a “recruit-by-genotype” approach to address biological questions related to the cross-talk between adipose tissue and vascular/myocardial redox signalling in human cardiovascular disease.

We are also using state-of-the-art non-invasive imaging techniques (advanced ultrasound and CT imaging techniques) to study the structure and function of the cardiovascular system and explore its interactions with the adipose tissue. This programme of work led to the recent discovery of the "inside-to-outside" signals from the human cardiovascular system to the adipose tissue, and allowed the development of new clinical applications of cardiovascular imaging.

Since 2015, the group runs the Oxford Cardiovascular Computed Tomography programme, in partnership with the Manor Hospital, supporting the use of state-of-the-art cardiovascular CT imaging by groups within the University of Oxford. The group is using artificial intellience and machine learning approaches to analyse radiotranscriptomic signatures that lead to the develpment of new imaging biomarkers. A recent example is that of the develpment of Fat Attenuation Index (FAI), a new biomarker that detects inflammation in the human coronary arteries by analysing the changes of weighed CT attenuation of perivascular adipose tissue (Science Transl Med 2017). FAI has striking predictive value for cardiac mortality and acute coronary events, as demonstrated in a large prospective clinical study (CRISP-CT) organised together with Erlangen University (Germany) and Cleveland Clinic (USA) (Lancet 2018).    

Since 2015, the group runs the Oxford Academic cardiovascular Computed Tomography (OXACCT) programme, in partnership with the Manor Hospital, supporting the use of state-of-the-art cardiovascular CT imaging by groups within the University of Oxford. Within the group, we run the OXACCT Core Lab, peforming advanced analysis of cardiovascular CT images with specific focus on analysis of coronary plaques and perivascular adipose tissue.           

 Our group also organises small-scale randomised clinical trials that include extensive cardiovascular phenotyping, testing the effects of treatments (statins, folates etc) on the biology of the human vascular wall, myocardium and adipose tissue.