A proteomic approach to identify plasma proteins in patients with abdominal aortic aneurysm.

Our aim was to identify the key proteins involved in the pathogenesis of AAAs. To explore the possible pathogenetic mechanisms involved in AAA, we analyzed by proteomics modifications in plasma proteome of patients with AAA. Therefore, the present study analyzed the soluble plasma proteins using two dimensional electrophoresis (2-DE) and mass spectrometry (MS). We identified 33 protein spots, 31 of which show an up-regulation in AAA patients whilst the expression level of 2 protein spots is reduced. We confirm a number of biomarkers associated with AAA that have been previously identified by various authors. We identified a significant increase of a class of proteins such as fibrinogen, a1-antitrypsin and haptoglobin in plasma from AAA patients. The presence of these proteins in human AAA plasma may be related to the inflammatory processes active in these subjects. We have seen a negative correlation between the vitamin D-binding protein (DBP) and hemoglobin subunit b and AAA presence. DBP levels have been found to increase in AAA wall tissues by others and this discrepancy with our results could be due to the different analysis source. We wanted to analyze the factors measurable in plasma-associated rather than in tissue-associated markers because the application of circulating biomarkers in diagnostic laboratories would be relatively simple. DBP is very important for vascular remodelling and it may have an important role in the protection of vascular walls. In plasma tissue this protein reduces platelet aggregation and extends coagulation time. No one protein identified in this study has the biologic plausibility to be used singularly as a biomarker of aneurysmal disease due to inadequate specificity. The effect of using multiple biomarkers combined with clinical factors requires investigation in carefully designed population-based studies and these studies need to select the criteria of choice to define healthy controls very carefully. Clearer identification of various markers is needed, possibly using other proteomic techniques to screen for new candidates such as gel-free proteomic technology that enables us to handle larger groups of subject compared to gel-based proteomic technology.