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.
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 humanpatients 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 humanpatients, 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.
Authors: Chao Zhang; Dustin van der Voort; Hong Shi; Rongli Zhang; Yulan Qing; Shuichi Hiraoka; Minoru Takemoto; Koutaro Yokote; Joseph V Moxon; Paul Norman; Laure Rittié; Helena Kuivaniemi; G Brandon Atkins; Stanton L Gerson; Guo-Ping Shi; Jonathan Golledge; Nianguo Dong; Bernard Perbal; Domenick A Prosdocimo; Zhiyong Lin Journal: J Clin Invest Date: 2016-03-14 Impact factor: 14.808
Authors: Stephanie Morgan; Lang Ho Lee; Arda Halu; Jessica S Nicolau; Hideyuki Higashi; Anna H Ha; Jennifer R Wen; Alan Daugherty; Peter Libby; Scott J Cameron; Doran Mix; Elena Aikawa; A Phillip Owens; Sasha A Singh; Masanori Aikawa Journal: Front Cardiovasc Med Date: 2022-08-03
Authors: Christina Lund Kidholm; Hans Christian Beck; Julie Bukh Madsen; Nikolai Bjødstrup Palstrøm; Jes Sanddal Lindholt; Lars Melholt Rasmussen Journal: PLoS One Date: 2018-02-22 Impact factor: 3.240