Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

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-alpha1-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.

Multimodality Imaging Reveals a Gradual Increase in Matrix Metalloproteinase Activity at Aneurysmal Lesions in Live Fibulin-4 Mice

“…24,25 In addition to conventional imaging modalities (eg, ultrasound imaging or CT), new diagnostic tools that interrogate the aneurysmatic lesion potentially could serve to test pathophysiological hypotheses to identify the risk while the disease remains undetected and to evaluate novel therapeutic strategies. Accumulating evidence mainly from in vitro studies implicates the increase in MMP activity, most notably MMP-9, in the disease state.…”

Role of miR-195 in Aortic Aneurysmal Disease

“…Better diagnostic tools are urgently needed to identify patients at risk, monitor disease progression, and implement novel therapeutic and preemptive strategies. [25][26][27] Identification of those patients with AAAs at risk of subsequent expansion or rupture by a simple cheap noninvasive method of predicting subsequent AAA growth would meet an important clinical need. Once AAA is diagnosed, patients at high risk may be treated with earlier surgical repair to prevent rupture.…”

Predictors of Abdominal Aortic Aneurysm (AAA) Growth and AAA Rupture Risk Besides AAA Size: Fact or Fiction?

“…A biomarker able to predict AAA progression should meet 3 criteria: (1) biological plausibility, (2) correlation with AAA progression, and (3) prediction of treatment effect on disease outcome. 27 Circulating levels of several markers of extracellular matrix degeneration with biological plausibility have been correlated with AAA progression, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-a1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes, and tissue plasminogen activator. 27 Others supported that a quantitative 3-dimensional tortuosity index of the AAA shape 28 or the peak wall stress and the mean centerline curvature of the AAA 29 may be better predictors of the AAA rupture potential than AAA size.…”

“…Although promising results have been reported, no definite conclusions can be drawn yet. 27 Future studies are needed to evaluate and identify novel predictors of AAA growth and rupture risk.…”