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Relationship between aortic aneurysmal disease and air pollution using intraoperative samples from live donors and cadaveric organ donors (AAA-CLOUD) study

Multi-centre, Cohort study
Primary Investigator: Matt Bown
Funding: University of Leicester
Sponsor: University of Leicester
Start date: 01/06/2023
End date: 01/05/2028

Abdominal aortic aneurysm (AAA) represents about 1% of deaths in males over the age of 65, causing in excess of 4000 deaths each year within the UK. The majority of deaths are due to AAA rupture. The reasons for development of AAAs are complex with both environmental and genetic factors being to blame. AAA are known to be more common in persons of increasing age, male sex and Caucasian race as well as in those that smoke, are obese and suffer with hypertension (high blood pressure). Interestingly diabetes is thought to protect against the development of AAA. Although not yet fully understood, determining the biological reasons for AAA formation, growth and rupture are crucial since the only current treatment for AAA involves surgical repair and hence there is a need for the development of safe and effective drug therapies.

Air pollution is linked to the development and severity of several diseases, including cardiovascular disease (CVD), which accounts for more than half of the deaths attributed to air pollution. The World Health Organization (WHO) estimates that air pollution kills 7 million people per year worldwide and the Global Burden of Disease Project identifies it as the fourth leading cause of premature death. There is strong evidence that it is the small particulate component of air pollution that plays a key role in the processes causing ill health. In fact, there is recent evidence that this small particulate component of air pollution can make its way into the bloodstream and sit within the wall of blood vessels. Most of the air pollution research to date in the field of cardiovascular disease has concentrated on risks of myocardial infarction (heart attack) and stroke. There is almost no research on other important cardiovascular conditions such as aortic aneurysm, despite the biological likelihood that air pollution will worsen these conditions

Many of the organs that become available for transplant are from patients relatively free of pre-existing vascular disease, the cause of death in such cases is usually traumatic or neurological and often of sudden onset. This study will obtain specimens from those organ donors where consent has been given for use of surplus tissue, this will act as a control group. Aortic aneurysm samples will be obtained from live donors donating excess tissue during open surgical procedures of the aorta (consented prior to intervention).

The principal objective is to improve upon our understanding of disease mechanisms underlying aortic aneurysmal disease by comparing pathological aneurysm tissue (from open repair of the aorta) to healthy control aortic tissue obtained from renal transplant. Pathological tissue analysis will be used to look for evidence of pollutants within the vessel wall of aneurysms and compare this to ‘healthy’ controls, investigating the role of air pollution in aneurysm formation.