Our most recent Fellowships

Mr John Wild, University of Leicester

Investigating the genes involved in abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is a progressive ballooning of part of the aorta. The aorta is the largest artery in the body and extends from the heart to the abdomen, and it is within the abdomen that this enlargement occurs. The wall of the aneurysm is weaker than a normal artery and may not be able to withstand the pressure of blood inside. The main concern is that the aneurysm may rupture, in which case the severe internal bleeding may be fatal. The risk of AAA increases with age and is more common in men, affecting up to eight in 100 men over the age of 65. The reasons why some people develop aneurysms are unclear but our genetic make-up plays a part and there is a higher chance of developing AAA if a close relative has had the condition. It is thought that no single gene is the culprit in AAA and the interaction of several genes is likely to be involved.

Mr Wild will be investigating the differences in the genes of people who suffer from AAA and those who do not, helping to pin-point the genes which are linked to the development of aneurysms. Blood samples will be taken from volunteers and the DNA extracted and analysed. Tests will then be done to search for the presence of genetic markers in the DNA that are thought to be associated with AAA.

The walls of the aorta and other arteries contain elastin and collagen which are vital structural proteins that give the arterial walls strength and elasticity. ‘Cathepsins’ are enzymes which break down elastin and there is evidence that cathepsins may be linked with the development of AAA. The study will focus on a particular cathepsin gene and examine in detail the association between the gene and the susceptibility to AAA.

The findings from this project may help us to understand more about the causes of aneurysms and the processes which underlie the growth of aneurysms. This could lead to a test for highlighting those at risk of developing AAA and help in detecting and monitoring aneurysms, reducing the need for multiple hospital visits and costly radiological scans. By identifying those at risk at an earlier stage, patients may be given life-saving aneurysm repair surgery to prevent the weakened aorta from rupturing and leading to internal bleeding.
 

Dr Alexander Basran, University of Sheffield

Studying the links between lung infection and heart attack 

Atherosclerosis is the build-up of fatty deposits on the artery walls which can lead to angina and heart attack, and over recent years, evidence has grown that atherosclerosis is a complex process with inflammation playing a major role. Serious lung infections such as pneumonia can cause some people to have heart attacks and strokes but the reasons for this are unclear.

Dr Alexander Basran will be investigating the theory that white blood cells, which fight infection in the lung, may also accumulate in the arteries at sites of damage and atherosclerosis. These white blood cells release substances that cause inflammation and could make the atherosclerotic plaque in the artery more likely to break open and block the blood vessel, causing a heart attack or stroke.

The study will compare how inflammation happens in patients with pneumonia and healthy volunteers. Dr Basran will isolate the different types of white blood cells in blood samples taken during health and illness and examine how they release hormones when exposed to infection. The work will focus on ‘neutrophils’ - a particular type of white blood cell whose numbers rapidly and dramatically increase during infection and which is also thought to play an important part in atherosclerosis. In the second part of the project, with the help of healthy volunteers, Dr Basran will also study how the immune system responds to simulated infection at small sites in the skin using a unique technique which he has already developed. This involves injecting very small amounts of a bacterial toxin into the skin to stimulate the immune system and then taking biopsies, which will allow Dr Basran to study in detail the accumulation of neutrophils at the infection site and how they behave.

It is hoped that the findings will help to explain why infection is linked to heart attack and stroke, which remains a key question. This may help pave the way for the development of tests to identify patients with pneumonia most at risk of experiencing these cardiovascular problems, so that additional care can be given to prevent such complications.
 

Dr Lisa Crowley, Royal Derby Hospitals

Limiting heart problems in chronic kidney disease patients 

Some patients with kidney disease need dialysis to remove excess fluid and waste products which accumulate when the kidneys stop working. It is well recognised that these patients are much more likely to die from cardiovascular problems than from kidney failure, with death often due to heart failure or sudden cardiac death. Earlier studies by the Derby team have shown that the dialysis procedure itself may cause injury to the heart and fluid retention that occurs between dialysis sessions may also contribute to heart problems in these patients.

The composition of the fluid in the dialysis machine must be carefully controlled according to the needs of the patient, in order to draw out waste products and return the concentrations of other chemicals in the blood to healthy levels. This special dialysis fluid includes minerals and salt, however, the degree of fluid retention that the patient experiences may be affected by the amount of salt in the fluid.

Diabetic kidney disease is a common complication of diabetes and the most common reason for needing dialysis. Fluid retention may be made worse by high blood sugar levels in those patients with diabetes.

Dr Crowley will be studying whether changes to the dialysis procedure can limit the cardiovascular problems resulting from dialysis. The project will be divided into two parts designed to answer the following questions;
(1)    Does restricting salt in the dialysis fluid lead to less fluid retention between dialysis sessions?
(2)    Does controlling blood sugar levels lead to less fluid retention between dialysis sessions in patients with diabetes?

The dialysis patients will follow a low-salt diet and the amount of salt they receive on dialysis will gradually be reduced. Also, those patients with diabetes will have their blood sugar levels controlled using an insulin pump to try to further limit any fluid retention. Dr Crowley will then measure the degree of fluid retention between dialysis sessions and how much stress the heart is under during dialysis. Patients will be monitored very closely over a series of dialysis sessions and a scan called an echocardiogram will be performed before, during and after dialysis to assess the amount of injury to the heart.

The findings from this research may lead to a larger trial to investigate whether these simple changes to the dialysis procedure can reduce heart injury in dialysis patients. It is hoped that these techniques may improve the medical care given to kidney disease patients needing dialysis and reduce their risk of developing heart problems.