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Antoniades figure 1
Fig. 1: Cardiovascular phenotyping of the ox-HVF cohort: Phenotyping of ox-HVF cohort includes the use of non-invasive imaging (e.g. ultrasound). A study of endothelial function using Flow Mediated Dilatation of the brachial artery is shown above.

Our group undertakes translational research, moving from bench to bedside and vice versa. We have established one of the world’s most extensively phenotyped cohorts of patients undergoing cardiac surgery, The Oxford Heart Vessels & Fat (ox-HVF) cohort. The cohort includes more than 1500 patients undergoing cardiac surgery, who have been extensively phenotyped preoperatively using non-invasive imaging (Fig. 1).

During the surgery, samples of arteries, veins, right atrium appendage and adipose tissue from 5 different depots are harvested and partly used in bioassays aiming to characterise the paracrine/endocrine interactions between adipose tissue, the vascular wall and the heart. These samples form the ox-HVF bioresource, which is used for discovery research. When a new therapeutic target or diagnostic biomarker is discovered, then we apply our translational validation cycle that includes the use of:

 

Ex vivo models of human vessels, myocardium and adipose tissue.

By keeping human tissue alive, outside the human body, we apply various methodologies allowing better understanding of the way adipose tissue communicates with the cardiovascular system, in a patient-specific way (Fig. 2).

 Fig. 2: Ex vivo models of human vessels and ox-HVF:Vascular and myocardial samples obtained from patients undergoing cardiac surgery, are routinely used for vasomotor studies (top right) to obtain information of vascular function. Myocardial trabeculae are also used ex vivo to study myocardial contractility (bottom right).

Fig. 2: Ex vivo models of human vessels and ox-HVF: Vascular and myocardial samples obtained from patients undergoing cardiac surgery, are routinely used for vasomotor studies (top right) to obtain information of vascular function. Myocardial trabeculae are also used ex vivo to study myocardial contractility (bottom right).


Human adipose tissue secretome studies.

By applying co-culture methodologies we try to understand how diabetes or obesity/insulin resistance affect vascular or myocardial disease mechanisms via changes in adipose tissue secretome (Fig. 3).

 Fig. 3: Studying the interactions between adipose tissue and the vascular wall (tissue-tissue interactions):Adipose tissue is used in ex vivo co-culture models with human vessels, helps us to understand the principles governing the cross-talk between tissues in obesity/insulin resistance, diabetes and other conditions. Left: A biopsy of human adipose tissue infiltrated by CD68+ cells. Right: Superoxide anions detected using DHE staining of a human vessel, using confocal microscopy.

Fig. 3: Studying the interactions between adipose tissue and the vascular wall (tissue-tissue interactions) Adipose tissue is used in ex vivo co-culture models with human vessels, helps us to understand the principles governing the cross-talk between tissues in obesity/insulin resistance, diabetes and other conditions. Left: A biopsy of human adipose tissue infiltrated by CD68+ cells. Right: Superoxide anions detected using DHE staining of a human vessel, using confocal microscopy.


Patient-specific primary cell culture

To study how adipocytes isolated from human adipose tissue communicate with the vascular cells in a paracrine way. We routinely isolate pre-adipocytes from perivascular adipose tissue and vascular cells from the underlying human vessels, which are used in co-culture bioassays, enabling better understanding of the cell-cell communication signals between perivascular adipose tissue and the vascular wall (Fig. 4).

Fig. 4: Studying the interactions between adipocytes and vascular cells (cell-cell interactions): Adipocytes are isolated from human perivascular adipose tissue (left, with oil red O staining) and co-cultured with human vascular smooth muscle cells isolated from the underlying vessel (right). 

Fig. 4: Studying the interactions between adipocytes and vascular cells (cell-cell interactions) : Adipocytes are isolated from human perivascular adipose tissue (left, with oil red O staining) and co-cultured with human vascular smooth muscle cells isolated from the underlying vessel (right).


Transgenic experimental models

Generated in house to address specific questions raised through the translational programme of the group.

 

In vivo advanced imaging techniques

These enable the translation of our findings back to clinical applications. We have developed an advanced cardiac CT programme that uses information coming from the basic science lab, to develop new tools to image cardiovascular diseases, enabling improvement of risk stratification that will facilitate timely deployment of therapeutic and preventive strategies (fig. 5).

Fig. 5: Translating basic science findings back to clinical applications: Findings from our basic science/translational programme are directly translated into clinical applications. The group is developing novel imaging biomarkers characterising the quality of epicardial and perivascular adipose tissue, using computerised tomography angiography.

Fig. 5: Translating basic science findings back to clinical applications: Findings from our basic science/translational programme are directly translated into clinical applications. The group is developing novel imaging biomarkers characterising the quality of epicardial and perivascular adipose tissue, using computerised tomography angiography.  


Genetic tools

Used to identify patients with pre-specified genetic traits, enabling a “recruit-by-genotype” approach for prospective studies, to address biological questions related to the development of cardiovascular complications in obesity and diabetes.

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, identifying also a wide range of therapeutic targets, currently being validated.

Our group also organises mechanistic, 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. These clinical trials are always complemented with mechanistic studies using ex vivo models of human tissue, primary cell culture etc. 

 

 

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