The pathophysiologic basis of abdominal aortic aneurysm progression: a critical appraisal

Abstract

An aneurysm of the abdominal aorta is a common pathology and a major cause of sudden death in the elderly. Currently, abdominal aortic aneurysms (AAAs) can only be treated by surgery and an effective medical therapy is urgently missing. The pathophysiology of AAAs is complex and is believed to be best described as a comprehensive inflammatory response with an accompanying proteolytic imbalance; the latter being held responsible for the progressive weakening of the aortic wall. Remarkably, while interference in inflammatory and/or proteolytic cascades proves highly effective in preclinical studies, emerging clinical studies consistently fail to show a benefit. In fact, some anti-inflammatory interventions appear to adversely influence the disease process. Altogether, recent clinical observations not only challenge the prevailing concepts of AAA progression, but also raise doubt on the translatability of findings from rodent models for growing AAA.

Keywords:

• abdominal aneurysm
• fibrosis
• inflammation
• proteases
• therapy

Financial & competing interests disclosure

The author has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Key issues

• Current management of abdominal aortic aneurysm (AAA) disease fully depends on elective surgical repair of larger (viz. >55 mm) aneurysms.

• Issues with surgical repair remain. Open repair comes with significant morbidity and perioperative mortality. Endovascular AAA repair is not cost-effective, requires a life-long follow-up and has a similar long-term outcome to traditional open repair.

• Pharmaceutical strategies quenching AAA growth would greatly reduce the need for AAA repair.

• Most AAA patients die from cardiovascular disease and should be considered high-risk cardiovascular patients. Cardiovascular risk management does not influence AAA progression.

• Interference with vascular inflammation and/or protease activity quenches AAA formation in rodent models of the disease.

• All anti-inflammatory strategies tested in the clinical context have failed thus far. In fact, an accelerated AAA progression was observed during doxycycline therapy and profound immune suppression.

• Critical aspects of AAA progression are missing in the current rodent models of the disease.

• There is evidence for fibrosis and impaired compensatory repair in AAA disease. The impact of this merits further investigation.

Notes