New research shows that ‘good’ cholesterol may be able to prevent the growth of aneurysms – dangerous ‘ballooning’ in the wall of a blood vessel – in the body’s largest artery, the aorta. The researchers say that this discovery could lay the foundations for a future drug treatment for the condition, which is currently only treatable with surgery.
Abdominal aortic aneurysms can rupture and kill without warning. They are responsible for around 23,000 hospital visits and cause around 4,000 deaths each year in the UK. There are no therapeutic treatments for aneurysms. Patients are monitored until the aneurysm reaches what is considered to be a critical size where it is at significant risk of rupturing – 5cm in diameter – and then it is repaired by surgery. Each operation costs the NHS between £8,000 and £12,000.
In laboratory-based experiments, researchers from St George’s, University of London found that elevating the amount of high-density lipoprotein (HDL) cholesterol inhibited growth and reduced the size of an experimental aneurysm.
The researchers say that, in principle, if raising HDLs can be induced using a drug, then aneurysms could be treated from early diagnosis and it could negate the need for surgery.
This finding also potentially explains why patients with abdominal aortic aneurysms have lower concentrations of HDL.
Lead researcher Dr Gillian Cockerill from St George’s said: “More studies are needed but this finding could be the first step in finding a drug treatment for abdominal aortic aneurysms. It provides evidence to support the idea that a drug based on HDL raising could be a viable treatment option. Drug therapy is preferable to surgery. It is less distressing for the patient and could see their condition treated sooner.”
While more work is needed to understand the exact mechanism that enables this effect, their investigations show that raising HDL cholesterol influences changes in signals sent between cells, and programmed cell death (an essential part of the cell lifecycle in healthy organisms) in the aneurysmal artery. These changes were restricted to the specific region of the artery where HDL levels had been raised.
The researchers found that, by influencing these intracellular signals, introducing more HDLs reduced the activity of a protein known as ERK1/2, which is recognised for its cell growth properties, and promoted the death of those cells that were causing the aneurysm to grow.
So far, studies have focused on a model of the suprarenal area of the aorta (just above the kidney) and the infrarenal region, (the area that is just below the kidney and more commonly associated with aneurysm formation, accounting for approximately 90 per cent of aneurysms in humans). The researchers hope that this site-specific effect will help explain basic mechanisms of aneurysm formation.
Dr Cockerill says: “HDLs are a complex family of heterogeneous particles that may vary in composition, size and function. Whilst we have shown that elevating the concentration of the so-called ‘good-lipid’ can modulate site-specific cellular responses and inhibit aneurysm formation, it is important to learn more about changes that occur on HDL complexity in addition to the effects in the vascular responses that influence aneurysm development.”
The next phase of the investigations, which the researchers hope will begin in early 2013, will see the researchers test families of drugs that can elevate HDLs and reproduce the observed effects on aneurysms.
The findings are published online in the American Heart Association scientific journal Atherosclerosis Thrombosis and Vascular Biology.
For further information or to speak with the researcher, please contact Helena Clay in the St George’s, University of London press office on 020 8266 6831/07909 523 089 (out of hours) or hacly@sgul.ac.uk
St George’s, University of London (SGUL), established in 1733, is distinctive as the UK’s only independent medical and healthcare higher education institution. It benefits from strong links with the healthcare profession, including a shared site with St George’s Healthcare NHS Trust in Tooting, south west London.
SGUL is dedicated to the education and training of doctors, nurses, midwives, physician’s assistants, paramedics, physiotherapists, radiographers, social workers, healthcare and biomedical scientists. It attracts around 6,000 students, some of whom are taught in conjunction with Kingston University.
Research at SGUL has a UK and international focus and aims to improve prevention, diagnosis and treatment of disease in areas including infection and immunity, heart disease and stroke, and cell signalling. It also aims to enhance understanding of public health and epidemiology, clinical genetics, and social care sciences. www.sgul.ac.uk
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