Profile of Macrophages in Human Abdominal Aortic Aneurysms: A Transcriptomic, Proteomic, and Antibody Protein Array Study

Abdominal aortic aneurysms (AAA) are defined by an increased aortic diameter and characterized by impairment of the extracellular matrix, macrophages infiltration and decreased density of smooth muscle cells. Our aim is to identify the key molecules involved in the pathogenesis of AAAs. This study i...

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Bibliographic Details
Published in:Journal of proteome research 2010-07, Vol.9 (7), p.3720-3729
Main Authors: Lamblin, Nicolas, Ratajczak, Philippe, Hot, David, Dubois, Emilie, Chwastyniak, Maggy, Beseme, Olivia, Drobecq, Hervé, Lemoine, Yves, Koussa, Mohammad, Amouyel, Philippe, Pinet, Florence
Format: Article
Language:English
Subjects:
Antibodies - metabolism
Aortic Aneurysm, Abdominal - metabolism
Biomarkers
Blood Proteins - analysis
Blood Proteins - genetics
Blood Proteins - metabolism
Case-Control Studies
Cells, Cultured
Electrophoresis, Gel, Two-Dimensional
Gene Expression Profiling - methods
Humans
Macrophages - metabolism
Male
Oligonucleotide Array Sequence Analysis
Peripheral Vascular Diseases
Protein Array Analysis - methods
Proteins - analysis
Proteins - genetics
Proteins - metabolism
Proteome - analysis
Proteome - genetics
Proteome - metabolism
Reproducibility of Results
Statistics, Nonparametric
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Summary:Abdominal aortic aneurysms (AAA) are defined by an increased aortic diameter and characterized by impairment of the extracellular matrix, macrophages infiltration and decreased density of smooth muscle cells. Our aim is to identify the key molecules involved in the pathogenesis of AAAs. This study investigated transcriptomic and proteomic profiles of macrophages from AAA patients (>50 mm aortic diameter) (n = 24) and peripheral arterial occlusion (PAO) patients without AAA detected (n = 18), who both needed a surgery. An antibody protein microarray, generated by printing antibodies onto membranes against proteins selected from the transcriptomic and proteomic analysis, was performed to validate the proteins differentially expressed specifically in macrophages and plasma from the same patients. We found a restricted number of proteins differentially expressed between AAA and PAO patients: TIMP-3, ADAMTS5, and ADAMTS8 that differ significantly in plasma of AAA patients compared to PAO patients, as found in the macrophages. In contrast to plasma MMP-9, soluble glycoprotein V (sGPV) and plasmin-antiplasmin complex levels, plasma TIMP-3 levels were not correlated to AAA size but interestingly correlated to sGPV, a platelet activation marker. Combining transcriptomic and proteomic is a valid approach to identify diseases causing proteins and potential biomarkers.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr100250s