Translational Research Group - Current Projects
The Role of Androgens in Angiogenesis
In 2006, our group was awarded a Project Grant to study the role of male sex hormones (androgens) in angiogenesis. While men are more likely to develop coronary artery disease than women, men are also more likely to have a favourable outcome after a heart attack compared to women. This gender difference after heart attacks, suggests that sex hormones such as the androgens, may play a role in the reparative response after a heart attack.
In fact, there is evidence from some studies in cells and in animals that androgens increase blood vessel formation. We will study the effects of androgens on angiogenesis and in mobilising endothelial progenitor cells using human cells, animal studies and in a human clinical trial.
This research will help us further understand the differences between men and women in heart disease Heart Facts. It will also help us understand more about the risks/benefits of androgen replacement in older men. This work will be carried out in close collaboration with Prof David Celermajer of the Clinical Research Group.
Physiologic Assessment of the Microcirculation
The state of the coronary microcirculation is an important determinant of patient outcomes in a number of clinical settings, including acute coronary syndromes, percutaneous coronary interventions, and cardiac transplantation-related allograft vasculopathy. However, to date, a simple and reproducible invasive method for assessing the coronary microcirculation has been lacking. Current techniques for evaluating the coronary microcirculation are limited because they are cumbersome, qualitative, rely on complex analyses, or do not independently interrogate the coronary microcirculation.
In 2006, Dr. Ng also described a new method for assessing the state of the microcirculation of patients with coronary disease, findings of which were published in the journal, Circulation. As the microcirculation is the principal target of therapeutic angiogenesis, it is hoped that this work, carried out in conjunction with Dr. William Fearon at Stanford, will lead to new methods to monitor the effects of angiogenic treatments and also to identify those who may benefit from therapeutic angiogenesis.
Tissue Engineering New Biomaterials for Treating Cardiovascular Disease
A major interest of our group involves the development of new synthetic materials that can be effectively used for treatment of cardiovascular disease. Despite the increasing incidence of heart disease, there are few effective biomaterials currently available for clinical vascular applications, including vascular conduits for bypass grafting and endografts for minimally invasive bypass procedures. An established treatment for clinical manifestations of atherosclerosis is the insertion of bypass grafts around an occluded arterial segment. The most common vascular grafts used are saphenous vein or mammary artery from the patient. However, although the mammary artery provides a potentially durable conduit, it may not always be the proper size or length. Saphenous vein grafts are susceptible to accelerated atherosclerosis such that by 10 years after coronary bypass grafting, 70% of vein grafts are either occluded or critically stenosed. Furthermore, the supply of artery or vein may not be sufficient or suitable for multiple bypass or repeat procedures, necessitating the use of other materials.
Currently, the principal synthetic graft materials used are woven polyethylene tetraphtlate (Dacron) and expanded polytetrafluoroethylene (ePTFE). These graft materials are rigid compared to the host artery, thrombogenic and do not readily facilitate endothelialisation. While Dacron and ePTFE perform satisfactorily as large diameter high-flow grafts (e.g. aortic-iliac replacement grafts), their use as small diameter (<6mm) vascular conduits (e.g. coronary artery or peripheral bypass surgery) has been associated with extremely high failure rates, such that no synthetic grafts are currently effective for coronary grafting, the most common bypass procedure. By using new tissue engineering methods, our group seeks to develop synthetic bypass grafts that closely mimic the properties of the human artery. An effective synthetic vascular graft would revolutionise the treatment of cardiovascular disease, meeting a significant and critical unmet need.
