Objective:

Discovery of novel biomarkers for AAA growth prediction.

Background:

Novel biomarker of AAA growth is a recognized priority in research. Our prior work implicated intraluminal thrombus (ILT) in AAAs to be a potential source of systemic mediators during AAA progression. Here we applied a mass spectrometry proteomics pipeline to discover novel biomarkers for AAA growth prediction.

Methods:

Patients were prospectively recruited. Plasma samples were collected at baseline (n= 62). AAA growth was recorded at 12 months. In Experiment 1, plasma samples from the fastest and slowest growth patients (n= 10 each) were compared. In Experiment 2, plasma samples were collected before and at 10–12 weeks after surgery (n= 29). In Experiment 3, paired ILT and omental biopsies were collected intra-operatively during open surgical repair (n= 3). In Experiment 4, tissue secretome was obtained from ex-vivo culture of these paired tissue samples. Samples were subjected to a liquid chromatography tandem mass spectrometry workflow to discover novel biomarkers.

Results:

We discovered 3 proteins that are:(i) present in ILT;(ii) released by ILT;(iii) reduced in circulation after AAA surgery;(iv) differs between fast and slow growth AAAs. One of these is Attractin. Plasma Attractin correlates significantly with future AAA growth (Spearman r= 0.35, P< 0.005). Using Attractin and AAA diameter as input variables, the area under receiver operating characteristics for predicting no growth and fast growth or AAA at 12 months is 85% and 76%, respectively.

Conclusion:

We show that ILT of AAAs releases mediators during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.