O01 – Victor Janssen – Amsterdam UMC

Combined plasma and tissue proteomics reveal inverse inflammatory and structural protein profile in abdominal aortic aneurysm patients

Samenvatting:
Introduction
Abdominal aortic aneurysms (AAA) are dilations in the abdominal aorta that carry a risk of rupturing, an event with an exceedingly high mortality. Diagnoses are often incidental and consistent monitoring is challenging, underlining the need for better diagnostic methods, especially for early detection and disease progression. Improvements in our understanding of why some aneurysms grow more rapidly than others would contribute to addressing these challenges.
Methods
We performed LC-MS based proteomics on blood plasma and tissue samples from 27 patients. Per patient, average aneurysm growth rate was calculated over a maximum period of three years. An average AAA growth rate was determined based on literature and patients were stratified according to being faster or slower growing. The blood plasma samples were depleted before measurement and tissue samples were pre-processed by bead homogenization protocol. Label-free LC-MS measurements were performed through data-independent methods.
Result
Differentially abundant proteins in plasma and tissue were analyzed by gene set enrichment and the results represented as networks to capture underlying biological processes. In tissue, extracellular matrix production and inflammation were up in the fast growth group, but in plasma were up in the slow growth group. In tissue, this is due to enrichment of proteins related to neutrophil activity, and while a weak consistent profile could be measurement in blood, most immune-related proteins in blood originated from the complement cascade, which was enriched in the slow growth group. Furthermore, differences in proteins related to mitochondrial metabolism were also found in both tissue and blood plasma.
Conclusion
These results highlight differences in biological development between fast and slow growing aneurysms and give rise to hypothesis on what processes are relevant for rapid AAA growth.