Investigating the role of natriuretic peptides and neutral endopeptidase in abdominal aortic aneurysm: a novel pharmacological approach for therapy

Abdominal aortic aneurysm (AAA) is a life-threatening disease caused by weakening and 'ballooning' of the aorta, the body’s largest blood vessel. If the aorta ruptures, severe internal bleeding occur and is often fatal. Approximately 4% of men aged 65-74 years in England have an AAA. Although AAA is more common in men, women with the condition often experience faster progression with higher risk of rupture at smaller AAA sizes.  As there are no medications available to treat AAA, surgery is the only treatment option. Therefore, there is an urgent need to develop new therapies.  We have discovered that a naturally occurring molecule produced by the body called C-type natriuretic peptide (CNP) helps protect the aorta and may represent a new treatment approach. 

This project will investigate how CNP protect against AAA and whether increasing its activity could lead to a new treatment. The student will develop skills in cardiovascular physiology and pharmacology, animal models of disease, ultrasound imaging, molecular and cellular biology, flow cytometry, microscopy, data analysis, scientific communication and outreach activities. 

The specific aims are to: 
1.    Obtain key research skills and training, use experimental models of AAA to measure AAA growth using ultrasound imaging and investigate how loss of CNP in specific cells type influence AAA development (Year 1). 
2.    Identify the biological pathways through which CNP protects the aorta and determine whether increasing CNP activity can prevent, halt or slow AAA in experimental models (Year 2-3). 
3.    Define the cellular mechanisms underlying the protective effects of CNP and examine aortic tissue and blood samples from AAA to confirm clinical relevance (Year 3-4). 

Ultimately, this work has strong translational potential because it will evaluate an existing class of drugs that increase natriuretic peptide activity and could be repurposed for AAA. This unique approach may reduce the need for surgery and improve outcomes for AAA patients.