Institute of Genetic Medicine

Staff Profile

Professor Helen Arthur

Professor of Cardiovascular Biology

Research

Research Interests

TGFβ Receptors in Cardiovascular Development and Disease

 The formation of new blood vessels, angiogenesis, is an essential developmental process that is also a target for treating many major diseases. For example, coronary heart disease causes the obstruction of blood vessels supplying heart tissue, leading to cardiac cell death. Here, increasing angiogenesis can re-establish the blood supply to minimise heart damage.

 Angiogenesis is regulated by a number of molecular signalling pathways and our work revolves around receptors in the TGFβ family signalling pathway. The importance of the TGFβ family of ligands in regulating angiogenesis and cardiovascular development was established in human genetic studies where inherited mutations in several TGFβ receptors leads to congenital cardiovascular abnormalities. For example, mutations in the receptors, endoglin or activin like kinase-1 (ACVRL1), are associated with the inherited bleeding disorder, Hereditary Haemorrhagic Telangiectasia (HHT).

 Using a combination of mouse genetics and cell culture systems, we have shown that endoglin is essential for cardiovascular development, is dynamically regulated during angiogenesis, and that depletion of endoglin in the context of an angiogenic trigger (such as developmental angiogenesis or inflammation) leads to arteriovenous malformations, a major clinical feature of HHT disease. We have shown that adult heart cells, cultured from biopsies and known as cardiospheres, contribute to the repair of heart function following myocardial infarction (a heart attack). We have shown that endoglin expressed by cardiosphere derived cells is essential for promoting angiogenesis in the ischaemic heart.

 More recently our work is addressing the problems caused by ischaemia reperfusion (I/R) injury in the heart. This injury occurs in acute heart attack patients who are successfully treated by an interventional cardiologist to re-open a blocked coronary artery. Much of the patient’s ischaemic myocardium can be saved by this rapid clinical intervention. However, the I/R injury that follows is due to inflammatory cells that invade the injured part of the heart and contribute to further damage. Suppressing this I/R response will improve outcomes for heart patients. We have shown that TGFbeta therapy is effective in reducing this injury and are currently investigating mechanisms that underlie this protective response and whether this therapy can be used in heart attack patients. In addition, in collaborative studies, we are investigating whether fractalkine, a protein that is dynamically regulated in cardiac I/R injury in patients, can be used as a target for therapy.

 Our goals in both HHT and heart attack patients is to use preclinical models to better understand disease mechanisms in order to inform the development of  improved therapies for patients.

Research Team  

Lilia Dragonova BSc
BHF PhD student

Darroch Hall BSc PhD
BHF Technician

Sarah Marsh BSc
MRC DTP PhD student

Rachel Redgrave BSc PhD
BHF Research Associate

Esha Singh MSc
BHF Research Assistant

Simon Tual-Chalot PhD
BHF Research Associate


 


Publications