An update on the etiology of abdominal aortic aneurysms: implications for future diagnostic testing

Abstract

Abdominal aortic aneurysm (AAA) disease is multifactorial with both environmental and genetic risk factors. The current research in AAA revolves around genetic profiles and expression studies in both human and animal models. Variants in genes involved in extracellular matrix degradation, inflammation, the renin–angiotensin system, cell growth and proliferation and lipid metabolism have been associated with AAA using a variety of study designs. However, the results have been inconsistent and without a standard animal model for validation. Thus, despite the growing body of knowledge, the specific variants responsible for AAA development, progression and rupture have yet to be determined. This review explores some of the more significant genetic studies to provide an overview of past studies that have influenced the current understanding of AAA etiology. Expanding our understanding of disease pathogenesis will inform research into novel diagnostics and therapeutics and ultimately to improve outcomes for patients with AAA.

Keywords:

• AAA
• abdominal aortic aneurysm
• aneurysm
• aneurysm disease
• cardiovascular disease
• genetics
• genotyping

Financial & competing interests disclosure

ML Marin has acted as a consultant for WL Gore. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Key issues

• Current treatment options for AAA include monitoring, endovascular repair and open repair; no effective medical treatments have been validated.

• The multiplicity AAA-associated variants in different pathways suggest a complex, multifactorial disease, which possibly represents a heterogeneous group of diseases naively lumped together and given the final diagnosis of AAA.

• A number of clinical trials have been conducted on protease inhibitors, renin–angiotensin system (RAS) acting drugs, and lipid metabolism modulators like statins using various animal models of AAA and human trials, but have yet to be validated or gain US FDA approval.

• Animal models for AAA need to be standardized, characterized and validated against the human disease.

• Better-matched control populations need to be used to determine variants associated with AAA compared with those associated with other comorbidities and risk factors.

• Whole genome sequencing in conjunction with other methods is necessary to determine the etiology of AAA.

• Greater understanding of the etiology of development, progression and rupture could alter the therapeutic decision matrix. Patients with validated variants for increased risk of AAA or of ruptured AAA could be monitored more closely and/or intervened on earlier minimizing the risk of ruptured aneurysms.