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Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Nature Reviews Cardiology volume 6, pages 464–474 (2009)Cite this article

Abstract

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase–α1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin–antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

Key Points

  • Abdominal aortic aneurysm has complex pathophysiology

  • Progression of abdominal aortic aneurysm is influenced by many factors

  • The natural history of abdominal aortic aneurysm differs between individual patients

  • An ideal biomarker of abdominal aortic aneurysm progression should have a causal relationship to the disease and should be responsive to intervention

  • Circulating levels of markers of extracellular matrix degeneration (elastin peptides, PIIINP, elastase–A1AT complexes, MMP-9, cystatin C, PAPs and tPA) have biological plausibility and have been reported as potential biomarkers

  • There is a need for a prospective, standardized study to investigate a set of plausible biomarkers for prediction of abdominal aortic aneurysm progression

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Figure 1: Abdominal aortic aneurysm (AAA) histology.
Figure 2: Stages of aneurysmal disease.
Figure 3: Three major protease families.

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  1. Maastricht University Medical Center, Maastricht, The Netherlands

    Femke A. M. V. I. Hellenthal, Willem A. Buurman, Will K. W. H. Wodzig & Geert Willem H. Schurink

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Hellenthal, F., Buurman, W., Wodzig, W. et al. Biomarkers of AAA progression. Part 1: extracellular matrix degeneration. Nat Rev Cardiol 6, 464–474 (2009). https://doi.org/10.1038/nrcardio.2009.80

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