Proteomic and genomic analyses suggest the association of Apolipoprotein C1 with abdominal aortic aneurysm

Moxon, Joseph V., Liu, Dawei, Moran, Corey S., Crossman, David J., Krishna, Smriti M., Yonglitthipagon, Ponlapat, Emeto, Theophilus I., Morris, Dylan R., Padula, Matthew P., Mulvenna, Jason P., Rush, Catherine M., and Golledge, Jonathan (2014) Proteomic and genomic analyses suggest the association of Apolipoprotein C1 with abdominal aortic aneurysm. Proteomics Clinical Applications, 8 (10). pp. 762-772.

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Purpose: Abdominal aortic aneurysm (AAA) is an important cause of mortality in the elderly. Mouse models are widely used to investigate AAA pathogenesis but their suitability for biomarker discovery is unexplored.

Experimental design: We conducted a three-phase study. Phase 1: Aortas from angiotensin- II-infused apolipoprotein E deficient (ApoE−/−) mice with and without AAA were assessed via iTRAQ and analyzed in silico to identify potential circulating markers. Microarray data from ApoE−/− mice and human patients were analyzed in parallel. Phase 2: Putative markers were compared between datasets to shortlist common candidates. Phase 3: The relationship of two shortlisted markers and AAA presence was assessed.

Results: iTRAQ identified eight proteins with biomarker potential. Microarray data identified 72 and 96 potential biomarkers from ApoE−/− mice and human patients, respectively. All three datasets suggested apolipoprotein C1 (ApoC1) as a marker for AAA; microarray data identified matrix metalloproteinase 9 (MMP9) as a second potential marker. Plasma ApoC1 and MMP9 concentrations positively correlated with AAA diameter in ApoE−/− mice.

Conclusions and clinical relevance: ApoC1 may be a novel biomarker for AAA.

Item ID: 33414
Item Type: Article (Research - C1)
ISSN: 1862-8346
Keywords: abdominal aortic aneurysm; apolipoprotein C1; biomarker; mouse model
Funders: James Cook University, Australian National Health and Medical Research Council (NHMRC), Townsville Hospital Private Practice Trust Fund, Queensland Government
Date Deposited: 11 Jun 2014 00:16
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060102 Bioinformatics @ 40%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060109 Proteomics and Intermolecular Interactions (excl Medical Proteomics) @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 30%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 80%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 20%
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