Abstract
BackgroundAbdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1–4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions.Methodology/Principal FindingsPooled human plasma samples of 17 AAA and 17 control patients were depleted of the most abundant proteins and compared using a data-independent shotgun proteomic strategy, Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with spectral counting and isobaric tandem mass tags. Both quantitative methods collectively identified 80 proteins as statistically differentially abundant between AAA and control patients. Among differentially abundant proteins, a subgroup of 19 was selected according to Gene Ontology classification and implication in AAA for verification by Western blot (WB) in the same 34 individual plasma samples that comprised the pools. From the 19 proteins, 12 were detected by WB. Five of them were verified to be differentially up-regulated in individual plasma of AAA patients: adiponectin, extracellular superoxide dismutase, protein AMBP, kallistatin and carboxypeptidase B2.Conclusions/SignificancePlasma depletion of high abundance proteins combined with quantitative PAcIFIC analysis offered an efficient and sensitive tool for the screening of new potential biomarkers of AAA. However, WB analysis to verify the 19 PAcIFIC identified proteins of interest proved inconclusive save for five proteins. We discuss these five in terms of their potential relevance as biological markers for use in AAA screening of population at risk.
Highlights
Abdominal aortic aneurysm (AAA) is one of the leading causes of death in industrialized countries where a growing percentage of the population is over 65 years of age [1]
Clinical population There was no statistically significant difference between the baseline characteristics of AAA and control patients selected in this study, except for the presence or absence of AAA (Table 1)
In the AAA pooled plasma sample, 311 proteins were identified as multiple hits while 687 proteins were identified as single hits
Summary
Abdominal aortic aneurysm (AAA) is one of the leading causes of death in industrialized countries where a growing percentage of the population is over 65 years of age [1]. AAA is a vascular pathology characterized by an increase of aorta diameter to at least 1.5 times the diameter of a standard reference or $30 mm of infrarenal aorta diameter, and a loss of parallelism of the aortic wall at the infrarenal region. Mortality occurs in 65–75% of patients before they arrive at hospital [3] This high mortality is largely due to the fact that the vast majority of AAA patients are asymptomatic and diagnosis is normally not possible prior to rupture [4]. Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (.1.5 times normal) and loss of parallelism. This disease is responsible for 1–4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions
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